肌动蛋白参与基因转录延伸的机制的研究
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摘要
肌动蛋白不仅作为细胞质骨架的主要成分存在于真核细胞内,而且还作为一种细胞核蛋白,对基因的转录进行调控。近期实验报道,在基因的转录过程中,细胞核肌动蛋白分别作为染色质改构复合物,转录前起始复合物和信使核糖核蛋白的组分参与了3种真核生物RNA聚合酶的转录调控。实验证明,肌动蛋白在3种真核生物RNA聚合酶早期的转录中是通用的,而且在转录过程中肌动蛋白与转录装置是直接结合的。此外体内实验证明,在RNA聚合酶Ⅱ依赖的转录过程中,肌动蛋白与特定系列的前信使核糖核蛋白结合形成复合物,并以这个复合物作为一个分子平台招募一些组蛋白修饰酶对转录进行调控。
肌动蛋白已经被证明参与了真核生物RNA聚合酶的转录,但是在这一过程中,肌动蛋白是以什么结构形式参与其中的仍然不清楚。近期有报道称,单体细胞核肌动蛋白参与了信号转导,同时另一实验证明,聚合形式的肌动蛋白和肌球蛋白的一种异形体(肌球蛋白Ⅰ)相结合,参与了RNA聚合酶Ⅰ所介导的基因转录。此外,对脱氧核糖核酸酶I(DNaseⅠ)的沉淀复合物进行亲和色谱分析显示,肌动蛋白与核糖核蛋白U (hnRNP U),组蛋白乙酰化转移酶PCAF和RNA聚合酶Ⅱ形成复合物。DNaseⅠ与单体肌动蛋白有很高的亲和性这一众所周知的事实说明了单体肌动蛋白参与这一过程。以上结果提示我们,应该对肌动蛋白究竟是以单体还是聚合形式在细胞核内行使功能进行进一步的研究。
在本文中,我们发现在转录延伸复合物中肌动蛋白与正性转录延伸因子P-TEFb的催化亚基,细胞周期依赖性激酶9(Cdk9)能够相互作用。免疫荧光和免疫沉淀实验证明,Cdk9通过T-loop上保守的186位苏氨酸与单体肌动蛋白相结合。过表达和体外激酶实验证明,单体肌动蛋白能够促进P-TEFb依赖的RNA聚合酶Ⅱ的C-末端结构域的磷酸化水平。体外转录实验表明,单体肌动蛋白与Cdk9之间的相互作用能够促进RNA聚合酶Ⅱ的转录延伸。我们利用染色质免疫沉淀实验和体外固定模板实验证明了肌动蛋白能够招募Cdk9到转录模板上。利用白细胞介素6(IL-6)诱导的p21基因表达体系进一步证实,肌动蛋白能够将Cdk9招募到内源基因上。而且我们发现肌动蛋白和Cdk9能够通过与组蛋白乙酰化转移酶p300之间的作用,促进组蛋白H3的乙酰化水平,并进而促进乙酰化的组蛋白H3结合到转录模板上。综上所述,我们的实验结果表明肌动蛋白通过招募Cdk9对RNA聚合酶Ⅱ的碳末端进行磷酸化参与转录延伸这一过程,并且在延伸的过程中促进染色质的改构,使得转录延伸能够顺利的进行。
Actin is not only a major cytoskeletal component in all eukaryotic cells but also a nuclear protein that plays a role in gene transcription. Recent reports have shown that in gene transcription, nuclear actin plays a key role as a component of chromatin remodeling complexes, transcription pre-initiation complex and messenger RNP (mRNP) particles associated with all three eukaryotic RNA polymerases (pol). Recent studies have suggested that actin, in direct contact with the transcription apparatus, is required in an early step of transcription that is common to all three eukaryotic RNA polymerases. In addition, there is evidence from in vivo studies that actin is involved in the transcription elongation of classⅡgenes. In this case, actin is bound to a specific subset of premessenger RNA binding proteins, and the actin–messenger RNP complex may constitute a molecular platform for recruitment of histone-modifying enzymes.
Actin has now been implicated in transcription by RNA polymerases, but the structural form it adopts in these processes remains unclear. Recently, a claim was made that monomeric nuclear actin plays a role in signal transduction; while a study of RNA polymeraseⅠtranscription has implicated polymeric actin, consorting with an isoform of its classical partner myosin. Moreover, actin in complex with hnRNP U, PCAF, and polⅡcan be coprecipitated by DNaseⅠaffinity chromatography, which, notoriously, has a high affinity for monomeric actin. It now seems reasonable to start thinking about functions for both monomeric and polymeric actin in the nucleus.
In this study, actin was found to interact with Cdk9, a catalytic subunit of P-TEFb, in elongation complexes (ECs). Using immunofluorescence and immunoprecipitation assays, Cdk9 was found to bind to G-actin through the conserved Thr-186 in the T-loop. Overexpression and in vitro kinase assays showed that G-actin promotes P-TEFb-dependent phosphorylation of the PolⅡC-terminal domain (CTD). An in vitro transcription experiment revealed that the interaction between G-actin and Cdk9 stimulated PolⅡtranscription elongation. ChIP and immobilized template assays indicated that actin recruited Cdk9 to a transcriptional template in vivo and in vitro. Using cytokine interleukin-6 (IL-6)-inducible p21 gene expression system, we revealed that actin recruited Cdk9 to endogenous gene. Moreover, overexpression of actin and Cdk9 increased histone H3 acetylation and acetylized histone H3 binding to a transcriptional template through the interaction with histone acetyltransferase, p300. Taken together, our results suggested that actin participates in transcription elongation by recruiting Cdk9 for phosphorylation of the PolⅡCTD, and the actin-Cdk9 interaction promotes chromatin remodeling.
肌动蛋白已经被证明参与了真核生物RNA聚合酶的转录,但是在这一过程中,肌动蛋白是以什么结构形式参与其中的仍然不清楚。近期有报道称,单体细胞核肌动蛋白参与了信号转导,同时另一实验证明,聚合形式的肌动蛋白和肌球蛋白的一种异形体(肌球蛋白Ⅰ)相结合,参与了RNA聚合酶Ⅰ所介导的基因转录。此外,对脱氧核糖核酸酶I(DNaseⅠ)的沉淀复合物进行亲和色谱分析显示,肌动蛋白与核糖核蛋白U (hnRNP U),组蛋白乙酰化转移酶PCAF和RNA聚合酶Ⅱ形成复合物。DNaseⅠ与单体肌动蛋白有很高的亲和性这一众所周知的事实说明了单体肌动蛋白参与这一过程。以上结果提示我们,应该对肌动蛋白究竟是以单体还是聚合形式在细胞核内行使功能进行进一步的研究。
在本文中,我们发现在转录延伸复合物中肌动蛋白与正性转录延伸因子P-TEFb的催化亚基,细胞周期依赖性激酶9(Cdk9)能够相互作用。免疫荧光和免疫沉淀实验证明,Cdk9通过T-loop上保守的186位苏氨酸与单体肌动蛋白相结合。过表达和体外激酶实验证明,单体肌动蛋白能够促进P-TEFb依赖的RNA聚合酶Ⅱ的C-末端结构域的磷酸化水平。体外转录实验表明,单体肌动蛋白与Cdk9之间的相互作用能够促进RNA聚合酶Ⅱ的转录延伸。我们利用染色质免疫沉淀实验和体外固定模板实验证明了肌动蛋白能够招募Cdk9到转录模板上。利用白细胞介素6(IL-6)诱导的p21基因表达体系进一步证实,肌动蛋白能够将Cdk9招募到内源基因上。而且我们发现肌动蛋白和Cdk9能够通过与组蛋白乙酰化转移酶p300之间的作用,促进组蛋白H3的乙酰化水平,并进而促进乙酰化的组蛋白H3结合到转录模板上。综上所述,我们的实验结果表明肌动蛋白通过招募Cdk9对RNA聚合酶Ⅱ的碳末端进行磷酸化参与转录延伸这一过程,并且在延伸的过程中促进染色质的改构,使得转录延伸能够顺利的进行。
Actin is not only a major cytoskeletal component in all eukaryotic cells but also a nuclear protein that plays a role in gene transcription. Recent reports have shown that in gene transcription, nuclear actin plays a key role as a component of chromatin remodeling complexes, transcription pre-initiation complex and messenger RNP (mRNP) particles associated with all three eukaryotic RNA polymerases (pol). Recent studies have suggested that actin, in direct contact with the transcription apparatus, is required in an early step of transcription that is common to all three eukaryotic RNA polymerases. In addition, there is evidence from in vivo studies that actin is involved in the transcription elongation of classⅡgenes. In this case, actin is bound to a specific subset of premessenger RNA binding proteins, and the actin–messenger RNP complex may constitute a molecular platform for recruitment of histone-modifying enzymes.
Actin has now been implicated in transcription by RNA polymerases, but the structural form it adopts in these processes remains unclear. Recently, a claim was made that monomeric nuclear actin plays a role in signal transduction; while a study of RNA polymeraseⅠtranscription has implicated polymeric actin, consorting with an isoform of its classical partner myosin. Moreover, actin in complex with hnRNP U, PCAF, and polⅡcan be coprecipitated by DNaseⅠaffinity chromatography, which, notoriously, has a high affinity for monomeric actin. It now seems reasonable to start thinking about functions for both monomeric and polymeric actin in the nucleus.
In this study, actin was found to interact with Cdk9, a catalytic subunit of P-TEFb, in elongation complexes (ECs). Using immunofluorescence and immunoprecipitation assays, Cdk9 was found to bind to G-actin through the conserved Thr-186 in the T-loop. Overexpression and in vitro kinase assays showed that G-actin promotes P-TEFb-dependent phosphorylation of the PolⅡC-terminal domain (CTD). An in vitro transcription experiment revealed that the interaction between G-actin and Cdk9 stimulated PolⅡtranscription elongation. ChIP and immobilized template assays indicated that actin recruited Cdk9 to a transcriptional template in vivo and in vitro. Using cytokine interleukin-6 (IL-6)-inducible p21 gene expression system, we revealed that actin recruited Cdk9 to endogenous gene. Moreover, overexpression of actin and Cdk9 increased histone H3 acetylation and acetylized histone H3 binding to a transcriptional template through the interaction with histone acetyltransferase, p300. Taken together, our results suggested that actin participates in transcription elongation by recruiting Cdk9 for phosphorylation of the PolⅡCTD, and the actin-Cdk9 interaction promotes chromatin remodeling.
引文
1 Orphanides, G., Lagrange, T., and Reinberg, D. 1996. The general transcription factors of RNA polymerase II. Genes & Dev 10: 2657–2683.
2 Goodrich, J.A. and Tjian, R. 1994. Transcription factors IIE and IIH and ATP hydrolysis direct promoter clearance by RNA polymerase II. Cell 77: 145–156.
3 Holstege, F.C., van der Vliet, P.C., and Timmers, H.T. 1996. Opening of an RNA polymerase II promoter occurs in two distinct steps and requires the basal transcription factors IIE and IIH. EMBO J 15: 1666–1677.
4 Kim, T.K., Ebright, R.H., and Reinberg, D. 2000. Mechanism of ATP-dependent promoter melting by transcription factor IIH. Science 288: 1418–1422.
5 Luse, D.S, Jacob, G.A. 1987. Abortive initiation by RNA polymerase II in vitro at the adenovirus 2 major late promoter. J Biol Chem 262: 14990–14997.
6 Holstege, FCP., Fiedler, U., Timmers, HTM. 1997. Three transitions in the RNA polymerase II transcription complex during initiation. Embo J 16: 7468–7480.
7 Zawel, L., Kumar, K.P., and Reinberg, D. 1995. Recycling of the general transcription factors during RNA polymerase II transcription. Genes & Dev 9: 1479–1490.
8 Yudkovsky, N., Ranish, J.A., and Hahn, S. 2000. A transcription reinitiation intermediate that is stabilized by activator. Nature 408: 225–229.
9 Robert, J., Sims, III., Rimma, B. and Danny, R. 2004. Elongation by RNA polymerase II: the short and long of it. Genes Dev 18: 2437-2468.
10 Orphanides, G., Reinberg, D. 2002. A unified theory of gene expression. Cell 108: 439–451.
11 Svejstrup, J.Q. 2004. The RNA polymerase II transcription cycle: cycling through chromatin. Biochim Biophys Acta 1677: 64–73.
12 Palancade, B., Bensaude, O. 2003. Investigating RNA polymerase II carboxylterminal domain (CTD) phosphorylation. Eur J Biochem. 270: 3859–3870.
13 Shilatifard, A., Conaway, R.C., Conaway, J.W. 2003. The RNA polymerase II elongation complex. Annu Rev Biochem 72:693–715.
14 Stiller, J.W., Hall, B.D. 2002. Evolution of the RNA polymerase II C-terminal domain. Proc Natl Acad Sci 99: 6091– 6096.
15 Nonet, M., Sweetser, D., Young, R.A. 1987. Functional redundancy and structural polymorphism in the large subunit of RNA polymerase II. Cell 50:909–915.
16 Allison, L.A., Wong, J.K., Fitzpatrick, V.D., Moyle, M., Ingles, C.J. 1988. The C-terminal domain of the largest subunit of RNA polymerase II of Saccharomyces cerevisiae, Drosophila melanogaster, and mammals: a conserved structure with an essential function. Mol Cell Biol 8: 321–329.
17 West, M.L., Corden, J.L. 1995. Construction and analysis of yeast RNA polymerase II CTD deletion and substitution mutations. Genetics 140: 1223–1233.
18 Meininghaus, M., Chapman, R.D., Horndasch, M., Eick, D. 2000. Conditional expression of RNA polymerase II in mammalian cells. Deletion of the carboxyl-terminal domain of the large subunit affects early steps in transcription. J Biol Chem 275:24375–24382.
19 Litingtung, Y., Lawler, A.M., Sebald, S.M., Lee, E., Gearhart, J.D., Westpha,l H., Corden, J.L. 1999. Growth retardation and neonatal lethality in mice with a homozygous deletion in the C-terminal domain of RNA polymerase II. Mol Gen Genet 261:100–105.
20 Fong, N., Bentley, D.L. 2001. Capping, splicing, and 3' processing are independently stimulated by RNA polymerase II: different functions for different segments of the CTD. Genes Dev 15:1783–1795.
21 Pinhero, R., Liaw, P., Bertens, K., Yankulov, K. 2004. Three cyclin-dependent kinases preferentially phosphorylate different parts of the C-terminal domain of the large subunit of RNA polymerase II. Eur J Biochem 271: 1004–1014.
22 Fong, N., Bird, G., Vigneron, M., Bentley, D.L. 2003. A 10 residue motif at the C-terminus of the RNA pol II CTD is required for transcription, splicing and 3' end processing. EMBO J 22: 4274–4282.
23 Proudfoot, N.J., Furger, A., Dye, M.J. 2002. Integrating mRNA processing with transcription. Cell 108: 501–512.
24 Hirose, Y., Manley, J.L. 2002. RNA polymerase II and the integration of nuclear events. Genes Dev 14: 1415–1429.
25 Fong, N., Bentley, D.L. 2001. Capping, splicing, and 3' processing are independently stimulated by RNA polymerase II: different functions for different segments of the CTD. Genes Dev 15: 1783–1795.
26 Shatkin, A.J., Manley, J.L. 2000. The ends of the affair: capping and polyadenylation. Nat Struct Biol 7: 838–842.
27 Pokholok, D.K., Hannett, N.M., Young, R.A. 2002. Exchange of RNA polymerase II initiation and elongation factors during gene expression in vivo. Mol Cell 9: 799–809.
28 Calvo, O., Manley, J.L. 2003.Strange bedfellows: polyadenylation factors at the promoter. Genes Dev 17: 1321–1327.
29 Ahn, S.H., Kim, M., Buratowski, S. 2004. Phosphorylation of serine 2 within the RNA polymerase II C-terminal domain couples transcription and 3' end processing. Mol Cell 13: 67–76.
30 Bentley, D. 2002. The mRNA assembly line: transcription and processing machines in the same factory. Curr Opin Cell Biol 14: 336–342.
31 Palancade, B., Bensaude, O. 2003. Investigating RNA polymerase II carboxylterminal domain (CTD) phosphorylation. Eur J Biochem 270: 3859–3870.
32 Pokholok, D.K., Hannett, N.M., Young, R.A. 2002. Exchange of RNA polymerase II initiation and elongation factors during gene expression in vivo. Mol Cell 9: 799–809.
33 Komarnitsky, P., Cho, E.J., Buratowsk,i S. 2000. Different phosphorylated forms of RNA polymerase II and associated mRNA processing factors during transcription. Genes Dev 14: 2452–2460.
34 Cho, E.J., Kobor, M.S., Kim, M., Greenblatt, J., Buratowski, S. 2001. Opposing effects of Ctk1 kinase and Fcp1 phosphatase at Ser 2 of the RNA polymerase II C-terminal domain. Genes Dev 15: 3319–3329.
35 Roy, R., Adamczewski, J.P., Seroz, T., Vermeulen, W., Tassan, J.P., Schaeffer, L., Nigg, E.A., Hoeijmakers, J.H., Egly, J.M. 1994. The MO15 cell cycle kinase is associated with the TFIIH transcription-DNA repair factor. Cell 79: 1093–1101.
36 Serizawa, H., Makela, T.P., Conaway, J.W., Conaway, R.C., Weinberg, R.A., Young, R.A. 1995. Association of Cdk-activating kinase subunits with transcription factor TFIIH. Nature 374: 280–282.
37 Wada, T., Orphanides, G., Hasegawa, J., Kim, D.K., Shima, D., Yamaguchi, Y., Fukuda, A., Hisatake, K., Oh, S., Reinberg, D., Handa, H. 2000. FACT relieves DSIF/NELF-mediated inhibition of transcriptional elongation and reveals functional differences between P-TEFb and TFIIH. Mol Cell 5: 1067–1072.
38 Yamaguchi, Y., Inukai, N., Narita, T., Wada, T., Handa, H. 2002. Evidence that negative elongation factor represses transcription elongation through binding to a DRB sensitivity-Inducing factor/RNA polymerase II complex and RNA. Mol Cell Biol 22: 2918–2927.
39 Proudfoot, N.J., Furger, A., Dye, M.J. 2002. Integrating mRNA processing with transcription. Cell 108: 501–512.
40 Komarnitsky, P., Cho, E.J., Buratowski, S. 2000. Different phosphorylated forms of RNA polymerase II and associated mRNA processing factors during transcription. Genes Dev 14: 2452–2460.
41 Cho, E.J., Takagi, T., Moore, C.R., Buratowski, S. 1997. mRNA capping enzyme is recruited to the transcription complex by phosphorylation of the RNA polymerase II carboxy-terminal domain. Genes Dev 11: 3319–3326.
42 Schroeder, S.C., Schwer, B., Shuman, S., Bentley, D. 2000. Dynamic association of capping enzymes with transcribing RNA polymerase II. Genes Dev. 14: 2435 2440.
43 Rodriguez, C.R., Cho, E.J., Keogh, M.C., Moore, C.L., Greenleaf, A.L., Buratowski, S. 2000. Kin28, the TFIIH-associated carboxy-terminal domain kinase, facilitates the recruitment of mRNA processing machinery to RNA polymerase II. Mol Cell Biol 20: 104–112.
44 Cho, E.J., Rodriguez, C.R., Takagi, T., Buratowski, S. 1998. Allosteric interactions between capping enzyme subunits and the RNA polymerase II carboxyterminal domain. Genes Dev 12: 3482–3487.
45 Ho, C.K., Shuman, S. 1998. Distinct roles for CTD Ser-2 and Ser-5 phosphorylation in therecruitment and allosteric activation of mammalian mRNA capping enzyme. Mol Cell 3: 405– 411.
46 Marshall, N.F., Price, D.H. 1995. Purification of P-TEFb, a transcription factor required for the transition into productive elongation. J Biol Chem 270: 12335–12338.
47 Price, D.H. 2000. P-TEFb, a cyclin-dependent kinase controlling elongation by RNA polymerase II. Mol Cell Biol 20: 2629–2634.
48 Peng, J., Marshal,l N.F., Price, D.H. 1998. Identification of a cyclin subunit required for the function of Drosophila P-TEFb. J Biol Chem 273: 13855–13860.
49 Pederson,T. 2000. Half a Century of“the nuclear matrix”. Mol Biol Cell 11: 799~805.
50 Egly, J.M., N.G. Miyamoto, V. Moncollin, and P. Chambon. 1984. Is actin a transcription initiation factor for RNA polymerase B? EMBO J 3: 2363–2371.
51 Scheer, U., H. Hinssen, W.W., Franke, and B.M. Jockusch. 1984. Microinjection of actin-binding proteins and actin antibodies demonstrates involvement of nuclear actin in transcription of lampbrush chromosomes. Cell 39: 111–122.
52 Pederson, T., and Aebi, U. 2002. Actin in the nucleus: what form and what for? J. Struct. Biol 140:3–9.
53 Luger, K., Mader, A.W., Richmond, R.K., Sargent, D.F., Richmond, T.J. 1997. Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 389: 251-260.
54 Imbalzano, A.N., Kwon, H., Green, M.R., Kingston, R.E. 1994. Facilitated binding of TATA-binding protein to nucleosomal DNA. Nature 370: 481-485.
55 Kingston, R.E., Narlikar, G.J. 1999. ATP-dependent remodeling and acetylation as regulators of chromatin fluidity. Genes Dev 13: 2339-2352.
56 Kornberg, R.D., Lorch, Y. 1999. Chromatin-modifying and -remodeling complexes. Curr Opin Genet Dev 9: 148-151.
57 Martens, J.A., Winston, F. 2003. Recent advances in understanding chromatin remodeling by Swi/Snf complexes. Curr Opin Genet Dev 13: 136-142.
58 Reinke, H., Horz, W. 2003. Histones are first hyperacetylated and then lose contact with the activated PHO5 promoter. Mol Cell 11: 1599-1607.
59 Olave, I. A., Reck-Peterson, S. L. & Crabtree, G. R. 2002. Nuclear actin and actin-related proteins in chromatin remodeling. Annu Rev Biochem 71: 755–781.
60 Zhao, K., W. Wang, O.J. Rando, Y. Xue, K. Swiderek, A. Kuo, and G.R. Crabtree. 1998. Rapid and phosphoinositol-dependent binding of the SWI/SNFlike BAF complex to chromatin after T lymphocyte receptor signaling. Cell 95:625–636.
61 Rando, O. J., Zhao, K., Janmey, P. & Crabtree, G. R.2002 Phosphatidylinositol-dependent actin filament binding by the SWI/SNF-like BAF chromatin remodeling complex. Proc Natl Acad Sci 99: 2824–2829.
62 Bettinger, B.T., D.M. Gilbert, and D.C. Amberg. 2004. Actin up in the nucleus. Nat. Rev. Mol. CellBiol 5:410–415.
63 Olave, I.A., S.L. Reck-Peterson, and G.R. Crabtree. 2002. Nuclear actin and actin-related proteins in chromatin remodeling. Annu Rev Biochem 71:755–781.
64 Percipalle, P., N. Fomproix, K. Kylberg, F. Miralles, B. Bjorkroth, B. Daneholt, and N. Visa. 2003. An actin-ribonucleoprotein interaction is involved in transcription by RNA polymerase II. Proc Natl Acad Sci 100: 6475–6480.
65 Sj?linder, M., P. Bj?rk, E. S?derberg, N. Sabri, A.K. ?stlund Farrants, and N. Visa. 2005. The growing pre-mRNA recruits actin and chromatinmodifying factors to transcriptionally active genes. Genes Dev 19: 1871–1884.
66 Kiesler, E., M.E. Hase, D. Brodin, and N. Visa. 2005. Hrp59, an hnRNP M protein in Chironomus and Drosophila, binds to exonic splicing enhancers and is required for expression of a subset of mRNAs. J Cell Biol 168: 1013–1025.
67 Percipalle, P., J. Zhao, B. Pope, A. Weeds, U. Lindberg, and B. Daneholt. 2001. Actin bound to the heterogeneous nuclear ribonucleoprotein hrp36 is associated with Balbiani ring mRNA from the gene to polysomes. J. Cell Biol 153: 229–236.
68 Kukalev, A., Y. Nord, C. Palmberg, T. Bergman, and P. Percipalle. 2005. Actin and hnRNP U cooperate for productive transcription by RNA polymerase II. Nat Struct Mol Biol 12: 238–244.
69 Martens, J.H.A., M. Verlaan, E. Kalkhoven, J.C. Dorsman, and A. Zantema. 2002. Scaffold/matrix attachment region elements interact with a p300-scaffold attachment factor A complex and are bound by acetylated nucleosomes. Mol Cell Biol 22: 2598–2606.
70 Philimonenko, V.V., Zhao, J., Iben, S., Dingova, H., Kysela, K., Kahle, M., Zentgraf, H., Hofmann, W.A., de Lanerolle, P., Hozak, P., et al. 2004. Nuclear actin and myosin I are required for RNA polymerase I transcription. Nat Cell Biol 6: 1165-1172.
71 Hu, P., Wu, S., Hernandez, N. 2004 A role for beta-actin in RNA polymerase III transcription. Genes Dev 18: 3010-3015.
72 Fomproix, N., Percipalle, P. 2004. An actin–myosin complex on actively transcribing genes. Exp Cell Res 294: 140–148.
73 Grummt I 2003. Life on a planet of its own: regulation of RNA polymerase I transcription in the nucleolus. Genes Dev 17: 1691–1702.
74 Blaine, T., Bettinger, David, M., Gilbert and David, C. Amberg. 2004. Actin up in the nucleus. Nat Rev Mol Cell Biol 5: 410-415.
75 Posern, G., A. Sotiropoulos, and R. Treisman. 2002. Mutant actins demonstrate a role for unpolymerized actin in control of transcription by serum response factor. Mol Biol Cell 13: 4167–4178.
76 Posern, G., F. Miralles, S. Guetller, and R. Treisman. 2004. Mutant actins that stabilize F-actin use distinct mechanisms to activate the SRF coactivator MAL. EMBO J 23: 3973–3983.
77 Miralles, F., Posern, G., Zaromytidou, A.I., and Treisman, R. 2003. Actin dynamics control SRF activity by regulation of its coactivator, MAL Cell 113: 329–342.
78 Vartiainen, M.K., S. Guetller, B. Larijani, and R. Treisman. 2007. Nuclear actin regulates dynamic subcellular localization and activity of the SRF cofactor MAL. Science 316: 1749–1752.
79 Ye, J., J. Zhao, U. Hoffmann-Rohrer, and I. Grummt. 2008. Nuclear myosin I and polymeric actin act as a molecular motor that drives RNA polymerase I transcription. Genes Dev 22: 322–330.
80 Price, D. H. 2000. P-TEFb, a cyclin-dependent kinase controlling elongation by RNA polymerase II. Mol Cell Biol 20: 2629-2634.
81 Jones, K.A. 1997. Taking a new TAK on Tat transactivation. Genes Dev 11: 2593- 2599.
82 Robert, J., Sims III, Rimma, B. and Danny, R. 2004. Elongation by RNA polymerase II: the short and long of it. Genes Dev 18: 2437-2468.
83 Barboric, M., Nissen, R.M., Kanazawa, S., Jabrane-Ferrat, N., and Peterlin, B.M. 2001. NF-kappaB binds P-TEFb to stimulate transcriptional elongation by RNA polymerase II. Mol Cell 8: 327–337.
84 Barboric, M., Nissen, R.M., Kanazawa, S., Jabrane-Ferrat, N., and Peterlin, B.M. 2001. NF-kappaB binds P-TEFb to stimulate transcriptional elongation by RNA polymerase II. Mol Cell 8: 327–337.
85 Simone, C., Bagella, L., Bellan, C., and Giordano, A. 2002. Physical interaction between pRb and cdk9/cyclinT2 complex. Oncogene 21: 4158–4165.
86 Zhou Q et al. 2006. Yin and Yang of P-TEFb regulation: implications for human immunodeficiency virus gene expression and global control of cell growth and differentiation. Microbiol Mol Biol Rev 70: 646-659.
87 Kanazawa, S., Okamoto, T., and Peterlin, B. M. 2000. Tat competes with CIITA for the binding to P-TEFb and blocks the expression of MHC class II genes in HIV infection. Immunity 12: 61-70.
88 Sano, M., Schneider, M.D. 2004. Cyclin-dependent kinase-9: an RNAPII kinase at the nexus of cardiac growth and death cascades. Circ Res 95: 867-876.
89 Chen, R., Yang, Z., and Zhou, Q. 2004. Phosphorylated positive transcription elongation factor b (P-TEFb) is tagged for inhibition through association with 7SK snRNA. J Biol Chem 279: 4153-4160.
90 Yang, Z., Yik, J.H.N., Chen, R., He, N., Jang, M.K., Ozato, K., and Zhou, Q. 2005. Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4. Mol Cell 19: 535–545.
91 Jang, M.K., Mochizuki, K., Zhou, M., Jeong, H.S., Brady, J.N., and Ozato, K. 2005. The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II dependent transcription. Mol Cell 19: 523–534.
92 Yik J.H.N., Chen, R., Nishimura, R., Jennings, J.L., Link, A.J., Zhou, Q. 2003. Inhibition of P-TEFb (CDK9/cyclin T) kinase and RNA polymerase II transcription by the coordinated actions of HEXIM1 and 7SK snRNA. Mol Cell 12: 971-982.
93 Yik, J.H.N., Chen, R., Pezda, a.c., and Zhou, Q. 2005. Compensatory contributions of HEXIM1 and HEXIM2 in maintaining the balance of active and inactive PTEFb complexes for control of transcription. J Biol Chem 280: 16368-16376.
94 Jeronimo, C. et al. 2007. Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme. Mol Cell 27: 262-274.
95 He, N., Pezda, A.C., and Zhou, Q. 2005. Modulation of a P-TEFb functional equilibrium for the global control of cell growth and differentiation. Mol Cell 280: 16368-16376.
96 Xue, Y. Yang, Z., Chen, R., and Zhou, Q. 2010. A capping-independent function of MePCE in stabilizing 7SK snRNA and facilitating the assembly of 7SK snRNP. Nucleic Acids Res 38: 360-369.
97 Nguyen, V.T., Kiss, T., Michels, A.A., and Bensaude, O. 2001. 7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes. Nature 414: 322–325.
98 Yang, Z., Zhu, Q., Luo, K., and Zhou, Q. 2001. The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription. Nature 414: 317–322.
99 Yik, J.H., Chen, R., Pezda, A.C., Samford, C.S., and Zhou, Q. 2004. A human immunodeficiency virus type 1 Tat-like arginine-rich RNA binding domain is essential for HEXIM1 to inhibit RNA polymerase II transcription through 7SK snRNA-mediated inactivation of P-TEFb. Mol Cell Biol 24: 5094–5105.
100 Hu, X., Chen, R. 2010. The function and regulation mechanism of P-TEFb. Chem of Life 3: 429-433.
101 Elmendorf, B. J. Shilatifard, A., Yan, Q., Conaway, J. W., and Conaway, R.C.. 2001. Transcription Factors TFIIF, ELL, and Elongin Negatively Regulate SII-induced Nascent Transcript Cleavage by Non-arrested RNA Polymerase II Elongation Intermediates. J Biol Chem 276: 23109-23114.
102 Deng. W., and Stefan, G.E. 2005. Roberts A core promoter element downstream of the TATA box that is recognized by TFIIB Genes & Dev 19: 2418-2423.
103 Baumli, S., Lolli, G., Lowe, E.D., et al. 2008. The structure of P-TEFb (CDK9/cyclin T1), its complex with flavopiridol and regulation by phosphorylation. EMBO J 27: 1907–1918.
104 Fong, Y.W., Zhou, Q. 2000. Relief of two built-In autoinhibitory mechanisms in P-TEFb is required for assembly of a multicomponent transcription elongation complex at the human immunodeficiency virus type 1 promoter. Mol Cell Biol 20: 5897-907.
105 Elemer, G.S. and Edgington, T.S. 1994. Microfilament reorganization is associated with functional activation of alpha M beta 2 on monocytic cells J Biol Chem 269: 3159-3166.
106 Bretscher, A., Drees, B., Harsay, E., Schott, D., and Wang, T. 1994. What are the basic functions of microfilaments? Insights from studies in budding yeast. J Cell Biol 126: 821-825.
107 Bubb, M.R., Spector, I., Beyer, B.B., and Fosen, K.M. 2000. Effects of jasplakinolide on the kinetics of actin polymerization: an explanation for certain in vivo observations. J Biol Chem 275: 5163-5170.
108 James, F.C., Michael, D. F. and Lin, S. 1981. Cytochalasin D inhibits actin polymerization andinduces depolymerization of actin filaments formed during platelet shape change. Nature 293: 302-305.
108 Teresita, B., Charles, A.O., Paula K.R., and Stavros, C.M. 1998. Transcriptional Activation of the p21WAF1,CIP1,SDI1 Gene by Interleukin-6 Type Cytokines. A PREREQUISITE FOR THEIR PRO-DIFFERENTIATING AND ANTI-APOPTOTIC EFFECTS ON HUMAN OSTEOBLASTIC CELLS J Biol Chem 273: 21137-21144.
109 Mellor, J. 2005. The dynamics of chromatin remodeling at promoters. Mol Cell 19: 147-157.
110 Saha, A., Wittmeyer, J., and Cairns, B. R. 2006. Chromatin remodelling: the industrial revolution of DNA around histones. Nat Rev Mol Cell Biol 7: 437-447.
111 Hirose, Y., and Ohkuma, Y. 2007. Phosphorylation of the C-terminal Domain of RNA Polymerase II Plays Central Roles in the Integrated Events of Eucaryotic Gene Expression. J Biochem 141: 601–608.
112 Yoichi, S., Tatsuya, M., Tomohide, T., Shinji, K., Hiromichi, W., Teruhisa, K., Masatoshi, F., Akira, S., Toru, K., and Koji, H. 2010. Cyclin-dependent Kinase-9 Is a Component of the p300/GATA4 Complex Required for Phenylephrine-induced Hypertrophy in Cardiomyocytes. J Biol Chem 258: 9556-9568.
113 Steven H. 2004. Structure and mechanism of the RNA Polymerase II transcription machinery. Nat Struct Mol Biol 11(5): 394–403.
114 Piergiorgio, P. and Neus, V. 2006. Molecular functions of nuclear actin in transcription. J Biol Chem 172: 967-971.
115 Ivan, A. Olave, S.L., Reck-Peterson and Gerald, R. Crabtree. 2002. Nuclear actin and actin-related proteins in chromatin remodeling. Annu Rev Biochem. 71: 755-781.
116 Neus Visa. 2005. Actin in transcription. EMBO reports 6: 218-219.
117 Blaine, T. B., David, M.G., and David, C.A. 2004. Actin up in the nucleus. Natrue 5: 410-415.
118 Wu, J. and Gerald, R.C. 2007. Nuclear Actin as Choreographer of Cell Morphology and Transcription. Science 317: 1710-1711.
119 Stuven, T., Hartmann, E., G?rlich, D. 2003. Exportin 6: A novel nuclear export receptor that is specific for profilin. actin complexes. EMBO J 22: 5928–5940.
120 McDonald, D., Carrero, G., Andrin, C., de Vries, G., Hendzel, M.J. 2006. Nucleoplasmicβ-actin exists in a dynamic equilibrium between low-mobility polymeric species and rapidly diffusing populations. J Cell Biol 13: 541–552.
121 Jockusch, B.M., Schoenenberger, C.A., Stetefeld, J., Aebi, U. 2006. Tracking down the different forms of nuclear actin. Trends Cell Biol 16:391–396.
122 Wu, X., Yoo, Y., Okuhama, N.N., Tucker, P.W., Liu, G., Guan, J.L. 2006. Regulation of RNA polymerase II-dependent transcription by N-WASP and its nuclear binding partners. Nat Cell Biol 8: 756–763.
123 Yoo, Y., Wu, X., and Guan, J.L. 2007. A novel role of the actin nucleating ARP2/3 complex in the regulation of RNA polymerase II dependent transcription. J Biol Chem 282: 7616–7623.
124 Vieu E, N Hernandez. 2006. Actin’s latest act: polymerizing to facilitate transcription? Nat Cell Biol 8: 650–651.
125 Obrdlik, A., Kukalev, A., Louvet, E., Farrants, A.K., Caputo, L., Percipalle, P. 2008. The histone acetyltransferase PCAF associates with actin and hnRNP U for RNA polymerase II transcription. Mol Cell Biol 28: 6342–6357.
126 Hartzog, G.A., Speer, J.L., Lindstrom, D.L. 2002. Transcript elongation on a nucleoprotein template. Biochim Biophys Acta 1577: 276–286.
2 Goodrich, J.A. and Tjian, R. 1994. Transcription factors IIE and IIH and ATP hydrolysis direct promoter clearance by RNA polymerase II. Cell 77: 145–156.
3 Holstege, F.C., van der Vliet, P.C., and Timmers, H.T. 1996. Opening of an RNA polymerase II promoter occurs in two distinct steps and requires the basal transcription factors IIE and IIH. EMBO J 15: 1666–1677.
4 Kim, T.K., Ebright, R.H., and Reinberg, D. 2000. Mechanism of ATP-dependent promoter melting by transcription factor IIH. Science 288: 1418–1422.
5 Luse, D.S, Jacob, G.A. 1987. Abortive initiation by RNA polymerase II in vitro at the adenovirus 2 major late promoter. J Biol Chem 262: 14990–14997.
6 Holstege, FCP., Fiedler, U., Timmers, HTM. 1997. Three transitions in the RNA polymerase II transcription complex during initiation. Embo J 16: 7468–7480.
7 Zawel, L., Kumar, K.P., and Reinberg, D. 1995. Recycling of the general transcription factors during RNA polymerase II transcription. Genes & Dev 9: 1479–1490.
8 Yudkovsky, N., Ranish, J.A., and Hahn, S. 2000. A transcription reinitiation intermediate that is stabilized by activator. Nature 408: 225–229.
9 Robert, J., Sims, III., Rimma, B. and Danny, R. 2004. Elongation by RNA polymerase II: the short and long of it. Genes Dev 18: 2437-2468.
10 Orphanides, G., Reinberg, D. 2002. A unified theory of gene expression. Cell 108: 439–451.
11 Svejstrup, J.Q. 2004. The RNA polymerase II transcription cycle: cycling through chromatin. Biochim Biophys Acta 1677: 64–73.
12 Palancade, B., Bensaude, O. 2003. Investigating RNA polymerase II carboxylterminal domain (CTD) phosphorylation. Eur J Biochem. 270: 3859–3870.
13 Shilatifard, A., Conaway, R.C., Conaway, J.W. 2003. The RNA polymerase II elongation complex. Annu Rev Biochem 72:693–715.
14 Stiller, J.W., Hall, B.D. 2002. Evolution of the RNA polymerase II C-terminal domain. Proc Natl Acad Sci 99: 6091– 6096.
15 Nonet, M., Sweetser, D., Young, R.A. 1987. Functional redundancy and structural polymorphism in the large subunit of RNA polymerase II. Cell 50:909–915.
16 Allison, L.A., Wong, J.K., Fitzpatrick, V.D., Moyle, M., Ingles, C.J. 1988. The C-terminal domain of the largest subunit of RNA polymerase II of Saccharomyces cerevisiae, Drosophila melanogaster, and mammals: a conserved structure with an essential function. Mol Cell Biol 8: 321–329.
17 West, M.L., Corden, J.L. 1995. Construction and analysis of yeast RNA polymerase II CTD deletion and substitution mutations. Genetics 140: 1223–1233.
18 Meininghaus, M., Chapman, R.D., Horndasch, M., Eick, D. 2000. Conditional expression of RNA polymerase II in mammalian cells. Deletion of the carboxyl-terminal domain of the large subunit affects early steps in transcription. J Biol Chem 275:24375–24382.
19 Litingtung, Y., Lawler, A.M., Sebald, S.M., Lee, E., Gearhart, J.D., Westpha,l H., Corden, J.L. 1999. Growth retardation and neonatal lethality in mice with a homozygous deletion in the C-terminal domain of RNA polymerase II. Mol Gen Genet 261:100–105.
20 Fong, N., Bentley, D.L. 2001. Capping, splicing, and 3' processing are independently stimulated by RNA polymerase II: different functions for different segments of the CTD. Genes Dev 15:1783–1795.
21 Pinhero, R., Liaw, P., Bertens, K., Yankulov, K. 2004. Three cyclin-dependent kinases preferentially phosphorylate different parts of the C-terminal domain of the large subunit of RNA polymerase II. Eur J Biochem 271: 1004–1014.
22 Fong, N., Bird, G., Vigneron, M., Bentley, D.L. 2003. A 10 residue motif at the C-terminus of the RNA pol II CTD is required for transcription, splicing and 3' end processing. EMBO J 22: 4274–4282.
23 Proudfoot, N.J., Furger, A., Dye, M.J. 2002. Integrating mRNA processing with transcription. Cell 108: 501–512.
24 Hirose, Y., Manley, J.L. 2002. RNA polymerase II and the integration of nuclear events. Genes Dev 14: 1415–1429.
25 Fong, N., Bentley, D.L. 2001. Capping, splicing, and 3' processing are independently stimulated by RNA polymerase II: different functions for different segments of the CTD. Genes Dev 15: 1783–1795.
26 Shatkin, A.J., Manley, J.L. 2000. The ends of the affair: capping and polyadenylation. Nat Struct Biol 7: 838–842.
27 Pokholok, D.K., Hannett, N.M., Young, R.A. 2002. Exchange of RNA polymerase II initiation and elongation factors during gene expression in vivo. Mol Cell 9: 799–809.
28 Calvo, O., Manley, J.L. 2003.Strange bedfellows: polyadenylation factors at the promoter. Genes Dev 17: 1321–1327.
29 Ahn, S.H., Kim, M., Buratowski, S. 2004. Phosphorylation of serine 2 within the RNA polymerase II C-terminal domain couples transcription and 3' end processing. Mol Cell 13: 67–76.
30 Bentley, D. 2002. The mRNA assembly line: transcription and processing machines in the same factory. Curr Opin Cell Biol 14: 336–342.
31 Palancade, B., Bensaude, O. 2003. Investigating RNA polymerase II carboxylterminal domain (CTD) phosphorylation. Eur J Biochem 270: 3859–3870.
32 Pokholok, D.K., Hannett, N.M., Young, R.A. 2002. Exchange of RNA polymerase II initiation and elongation factors during gene expression in vivo. Mol Cell 9: 799–809.
33 Komarnitsky, P., Cho, E.J., Buratowsk,i S. 2000. Different phosphorylated forms of RNA polymerase II and associated mRNA processing factors during transcription. Genes Dev 14: 2452–2460.
34 Cho, E.J., Kobor, M.S., Kim, M., Greenblatt, J., Buratowski, S. 2001. Opposing effects of Ctk1 kinase and Fcp1 phosphatase at Ser 2 of the RNA polymerase II C-terminal domain. Genes Dev 15: 3319–3329.
35 Roy, R., Adamczewski, J.P., Seroz, T., Vermeulen, W., Tassan, J.P., Schaeffer, L., Nigg, E.A., Hoeijmakers, J.H., Egly, J.M. 1994. The MO15 cell cycle kinase is associated with the TFIIH transcription-DNA repair factor. Cell 79: 1093–1101.
36 Serizawa, H., Makela, T.P., Conaway, J.W., Conaway, R.C., Weinberg, R.A., Young, R.A. 1995. Association of Cdk-activating kinase subunits with transcription factor TFIIH. Nature 374: 280–282.
37 Wada, T., Orphanides, G., Hasegawa, J., Kim, D.K., Shima, D., Yamaguchi, Y., Fukuda, A., Hisatake, K., Oh, S., Reinberg, D., Handa, H. 2000. FACT relieves DSIF/NELF-mediated inhibition of transcriptional elongation and reveals functional differences between P-TEFb and TFIIH. Mol Cell 5: 1067–1072.
38 Yamaguchi, Y., Inukai, N., Narita, T., Wada, T., Handa, H. 2002. Evidence that negative elongation factor represses transcription elongation through binding to a DRB sensitivity-Inducing factor/RNA polymerase II complex and RNA. Mol Cell Biol 22: 2918–2927.
39 Proudfoot, N.J., Furger, A., Dye, M.J. 2002. Integrating mRNA processing with transcription. Cell 108: 501–512.
40 Komarnitsky, P., Cho, E.J., Buratowski, S. 2000. Different phosphorylated forms of RNA polymerase II and associated mRNA processing factors during transcription. Genes Dev 14: 2452–2460.
41 Cho, E.J., Takagi, T., Moore, C.R., Buratowski, S. 1997. mRNA capping enzyme is recruited to the transcription complex by phosphorylation of the RNA polymerase II carboxy-terminal domain. Genes Dev 11: 3319–3326.
42 Schroeder, S.C., Schwer, B., Shuman, S., Bentley, D. 2000. Dynamic association of capping enzymes with transcribing RNA polymerase II. Genes Dev. 14: 2435 2440.
43 Rodriguez, C.R., Cho, E.J., Keogh, M.C., Moore, C.L., Greenleaf, A.L., Buratowski, S. 2000. Kin28, the TFIIH-associated carboxy-terminal domain kinase, facilitates the recruitment of mRNA processing machinery to RNA polymerase II. Mol Cell Biol 20: 104–112.
44 Cho, E.J., Rodriguez, C.R., Takagi, T., Buratowski, S. 1998. Allosteric interactions between capping enzyme subunits and the RNA polymerase II carboxyterminal domain. Genes Dev 12: 3482–3487.
45 Ho, C.K., Shuman, S. 1998. Distinct roles for CTD Ser-2 and Ser-5 phosphorylation in therecruitment and allosteric activation of mammalian mRNA capping enzyme. Mol Cell 3: 405– 411.
46 Marshall, N.F., Price, D.H. 1995. Purification of P-TEFb, a transcription factor required for the transition into productive elongation. J Biol Chem 270: 12335–12338.
47 Price, D.H. 2000. P-TEFb, a cyclin-dependent kinase controlling elongation by RNA polymerase II. Mol Cell Biol 20: 2629–2634.
48 Peng, J., Marshal,l N.F., Price, D.H. 1998. Identification of a cyclin subunit required for the function of Drosophila P-TEFb. J Biol Chem 273: 13855–13860.
49 Pederson,T. 2000. Half a Century of“the nuclear matrix”. Mol Biol Cell 11: 799~805.
50 Egly, J.M., N.G. Miyamoto, V. Moncollin, and P. Chambon. 1984. Is actin a transcription initiation factor for RNA polymerase B? EMBO J 3: 2363–2371.
51 Scheer, U., H. Hinssen, W.W., Franke, and B.M. Jockusch. 1984. Microinjection of actin-binding proteins and actin antibodies demonstrates involvement of nuclear actin in transcription of lampbrush chromosomes. Cell 39: 111–122.
52 Pederson, T., and Aebi, U. 2002. Actin in the nucleus: what form and what for? J. Struct. Biol 140:3–9.
53 Luger, K., Mader, A.W., Richmond, R.K., Sargent, D.F., Richmond, T.J. 1997. Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 389: 251-260.
54 Imbalzano, A.N., Kwon, H., Green, M.R., Kingston, R.E. 1994. Facilitated binding of TATA-binding protein to nucleosomal DNA. Nature 370: 481-485.
55 Kingston, R.E., Narlikar, G.J. 1999. ATP-dependent remodeling and acetylation as regulators of chromatin fluidity. Genes Dev 13: 2339-2352.
56 Kornberg, R.D., Lorch, Y. 1999. Chromatin-modifying and -remodeling complexes. Curr Opin Genet Dev 9: 148-151.
57 Martens, J.A., Winston, F. 2003. Recent advances in understanding chromatin remodeling by Swi/Snf complexes. Curr Opin Genet Dev 13: 136-142.
58 Reinke, H., Horz, W. 2003. Histones are first hyperacetylated and then lose contact with the activated PHO5 promoter. Mol Cell 11: 1599-1607.
59 Olave, I. A., Reck-Peterson, S. L. & Crabtree, G. R. 2002. Nuclear actin and actin-related proteins in chromatin remodeling. Annu Rev Biochem 71: 755–781.
60 Zhao, K., W. Wang, O.J. Rando, Y. Xue, K. Swiderek, A. Kuo, and G.R. Crabtree. 1998. Rapid and phosphoinositol-dependent binding of the SWI/SNFlike BAF complex to chromatin after T lymphocyte receptor signaling. Cell 95:625–636.
61 Rando, O. J., Zhao, K., Janmey, P. & Crabtree, G. R.2002 Phosphatidylinositol-dependent actin filament binding by the SWI/SNF-like BAF chromatin remodeling complex. Proc Natl Acad Sci 99: 2824–2829.
62 Bettinger, B.T., D.M. Gilbert, and D.C. Amberg. 2004. Actin up in the nucleus. Nat. Rev. Mol. CellBiol 5:410–415.
63 Olave, I.A., S.L. Reck-Peterson, and G.R. Crabtree. 2002. Nuclear actin and actin-related proteins in chromatin remodeling. Annu Rev Biochem 71:755–781.
64 Percipalle, P., N. Fomproix, K. Kylberg, F. Miralles, B. Bjorkroth, B. Daneholt, and N. Visa. 2003. An actin-ribonucleoprotein interaction is involved in transcription by RNA polymerase II. Proc Natl Acad Sci 100: 6475–6480.
65 Sj?linder, M., P. Bj?rk, E. S?derberg, N. Sabri, A.K. ?stlund Farrants, and N. Visa. 2005. The growing pre-mRNA recruits actin and chromatinmodifying factors to transcriptionally active genes. Genes Dev 19: 1871–1884.
66 Kiesler, E., M.E. Hase, D. Brodin, and N. Visa. 2005. Hrp59, an hnRNP M protein in Chironomus and Drosophila, binds to exonic splicing enhancers and is required for expression of a subset of mRNAs. J Cell Biol 168: 1013–1025.
67 Percipalle, P., J. Zhao, B. Pope, A. Weeds, U. Lindberg, and B. Daneholt. 2001. Actin bound to the heterogeneous nuclear ribonucleoprotein hrp36 is associated with Balbiani ring mRNA from the gene to polysomes. J. Cell Biol 153: 229–236.
68 Kukalev, A., Y. Nord, C. Palmberg, T. Bergman, and P. Percipalle. 2005. Actin and hnRNP U cooperate for productive transcription by RNA polymerase II. Nat Struct Mol Biol 12: 238–244.
69 Martens, J.H.A., M. Verlaan, E. Kalkhoven, J.C. Dorsman, and A. Zantema. 2002. Scaffold/matrix attachment region elements interact with a p300-scaffold attachment factor A complex and are bound by acetylated nucleosomes. Mol Cell Biol 22: 2598–2606.
70 Philimonenko, V.V., Zhao, J., Iben, S., Dingova, H., Kysela, K., Kahle, M., Zentgraf, H., Hofmann, W.A., de Lanerolle, P., Hozak, P., et al. 2004. Nuclear actin and myosin I are required for RNA polymerase I transcription. Nat Cell Biol 6: 1165-1172.
71 Hu, P., Wu, S., Hernandez, N. 2004 A role for beta-actin in RNA polymerase III transcription. Genes Dev 18: 3010-3015.
72 Fomproix, N., Percipalle, P. 2004. An actin–myosin complex on actively transcribing genes. Exp Cell Res 294: 140–148.
73 Grummt I 2003. Life on a planet of its own: regulation of RNA polymerase I transcription in the nucleolus. Genes Dev 17: 1691–1702.
74 Blaine, T., Bettinger, David, M., Gilbert and David, C. Amberg. 2004. Actin up in the nucleus. Nat Rev Mol Cell Biol 5: 410-415.
75 Posern, G., A. Sotiropoulos, and R. Treisman. 2002. Mutant actins demonstrate a role for unpolymerized actin in control of transcription by serum response factor. Mol Biol Cell 13: 4167–4178.
76 Posern, G., F. Miralles, S. Guetller, and R. Treisman. 2004. Mutant actins that stabilize F-actin use distinct mechanisms to activate the SRF coactivator MAL. EMBO J 23: 3973–3983.
77 Miralles, F., Posern, G., Zaromytidou, A.I., and Treisman, R. 2003. Actin dynamics control SRF activity by regulation of its coactivator, MAL Cell 113: 329–342.
78 Vartiainen, M.K., S. Guetller, B. Larijani, and R. Treisman. 2007. Nuclear actin regulates dynamic subcellular localization and activity of the SRF cofactor MAL. Science 316: 1749–1752.
79 Ye, J., J. Zhao, U. Hoffmann-Rohrer, and I. Grummt. 2008. Nuclear myosin I and polymeric actin act as a molecular motor that drives RNA polymerase I transcription. Genes Dev 22: 322–330.
80 Price, D. H. 2000. P-TEFb, a cyclin-dependent kinase controlling elongation by RNA polymerase II. Mol Cell Biol 20: 2629-2634.
81 Jones, K.A. 1997. Taking a new TAK on Tat transactivation. Genes Dev 11: 2593- 2599.
82 Robert, J., Sims III, Rimma, B. and Danny, R. 2004. Elongation by RNA polymerase II: the short and long of it. Genes Dev 18: 2437-2468.
83 Barboric, M., Nissen, R.M., Kanazawa, S., Jabrane-Ferrat, N., and Peterlin, B.M. 2001. NF-kappaB binds P-TEFb to stimulate transcriptional elongation by RNA polymerase II. Mol Cell 8: 327–337.
84 Barboric, M., Nissen, R.M., Kanazawa, S., Jabrane-Ferrat, N., and Peterlin, B.M. 2001. NF-kappaB binds P-TEFb to stimulate transcriptional elongation by RNA polymerase II. Mol Cell 8: 327–337.
85 Simone, C., Bagella, L., Bellan, C., and Giordano, A. 2002. Physical interaction between pRb and cdk9/cyclinT2 complex. Oncogene 21: 4158–4165.
86 Zhou Q et al. 2006. Yin and Yang of P-TEFb regulation: implications for human immunodeficiency virus gene expression and global control of cell growth and differentiation. Microbiol Mol Biol Rev 70: 646-659.
87 Kanazawa, S., Okamoto, T., and Peterlin, B. M. 2000. Tat competes with CIITA for the binding to P-TEFb and blocks the expression of MHC class II genes in HIV infection. Immunity 12: 61-70.
88 Sano, M., Schneider, M.D. 2004. Cyclin-dependent kinase-9: an RNAPII kinase at the nexus of cardiac growth and death cascades. Circ Res 95: 867-876.
89 Chen, R., Yang, Z., and Zhou, Q. 2004. Phosphorylated positive transcription elongation factor b (P-TEFb) is tagged for inhibition through association with 7SK snRNA. J Biol Chem 279: 4153-4160.
90 Yang, Z., Yik, J.H.N., Chen, R., He, N., Jang, M.K., Ozato, K., and Zhou, Q. 2005. Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4. Mol Cell 19: 535–545.
91 Jang, M.K., Mochizuki, K., Zhou, M., Jeong, H.S., Brady, J.N., and Ozato, K. 2005. The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II dependent transcription. Mol Cell 19: 523–534.
92 Yik J.H.N., Chen, R., Nishimura, R., Jennings, J.L., Link, A.J., Zhou, Q. 2003. Inhibition of P-TEFb (CDK9/cyclin T) kinase and RNA polymerase II transcription by the coordinated actions of HEXIM1 and 7SK snRNA. Mol Cell 12: 971-982.
93 Yik, J.H.N., Chen, R., Pezda, a.c., and Zhou, Q. 2005. Compensatory contributions of HEXIM1 and HEXIM2 in maintaining the balance of active and inactive PTEFb complexes for control of transcription. J Biol Chem 280: 16368-16376.
94 Jeronimo, C. et al. 2007. Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme. Mol Cell 27: 262-274.
95 He, N., Pezda, A.C., and Zhou, Q. 2005. Modulation of a P-TEFb functional equilibrium for the global control of cell growth and differentiation. Mol Cell 280: 16368-16376.
96 Xue, Y. Yang, Z., Chen, R., and Zhou, Q. 2010. A capping-independent function of MePCE in stabilizing 7SK snRNA and facilitating the assembly of 7SK snRNP. Nucleic Acids Res 38: 360-369.
97 Nguyen, V.T., Kiss, T., Michels, A.A., and Bensaude, O. 2001. 7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes. Nature 414: 322–325.
98 Yang, Z., Zhu, Q., Luo, K., and Zhou, Q. 2001. The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription. Nature 414: 317–322.
99 Yik, J.H., Chen, R., Pezda, A.C., Samford, C.S., and Zhou, Q. 2004. A human immunodeficiency virus type 1 Tat-like arginine-rich RNA binding domain is essential for HEXIM1 to inhibit RNA polymerase II transcription through 7SK snRNA-mediated inactivation of P-TEFb. Mol Cell Biol 24: 5094–5105.
100 Hu, X., Chen, R. 2010. The function and regulation mechanism of P-TEFb. Chem of Life 3: 429-433.
101 Elmendorf, B. J. Shilatifard, A., Yan, Q., Conaway, J. W., and Conaway, R.C.. 2001. Transcription Factors TFIIF, ELL, and Elongin Negatively Regulate SII-induced Nascent Transcript Cleavage by Non-arrested RNA Polymerase II Elongation Intermediates. J Biol Chem 276: 23109-23114.
102 Deng. W., and Stefan, G.E. 2005. Roberts A core promoter element downstream of the TATA box that is recognized by TFIIB Genes & Dev 19: 2418-2423.
103 Baumli, S., Lolli, G., Lowe, E.D., et al. 2008. The structure of P-TEFb (CDK9/cyclin T1), its complex with flavopiridol and regulation by phosphorylation. EMBO J 27: 1907–1918.
104 Fong, Y.W., Zhou, Q. 2000. Relief of two built-In autoinhibitory mechanisms in P-TEFb is required for assembly of a multicomponent transcription elongation complex at the human immunodeficiency virus type 1 promoter. Mol Cell Biol 20: 5897-907.
105 Elemer, G.S. and Edgington, T.S. 1994. Microfilament reorganization is associated with functional activation of alpha M beta 2 on monocytic cells J Biol Chem 269: 3159-3166.
106 Bretscher, A., Drees, B., Harsay, E., Schott, D., and Wang, T. 1994. What are the basic functions of microfilaments? Insights from studies in budding yeast. J Cell Biol 126: 821-825.
107 Bubb, M.R., Spector, I., Beyer, B.B., and Fosen, K.M. 2000. Effects of jasplakinolide on the kinetics of actin polymerization: an explanation for certain in vivo observations. J Biol Chem 275: 5163-5170.
108 James, F.C., Michael, D. F. and Lin, S. 1981. Cytochalasin D inhibits actin polymerization andinduces depolymerization of actin filaments formed during platelet shape change. Nature 293: 302-305.
108 Teresita, B., Charles, A.O., Paula K.R., and Stavros, C.M. 1998. Transcriptional Activation of the p21WAF1,CIP1,SDI1 Gene by Interleukin-6 Type Cytokines. A PREREQUISITE FOR THEIR PRO-DIFFERENTIATING AND ANTI-APOPTOTIC EFFECTS ON HUMAN OSTEOBLASTIC CELLS J Biol Chem 273: 21137-21144.
109 Mellor, J. 2005. The dynamics of chromatin remodeling at promoters. Mol Cell 19: 147-157.
110 Saha, A., Wittmeyer, J., and Cairns, B. R. 2006. Chromatin remodelling: the industrial revolution of DNA around histones. Nat Rev Mol Cell Biol 7: 437-447.
111 Hirose, Y., and Ohkuma, Y. 2007. Phosphorylation of the C-terminal Domain of RNA Polymerase II Plays Central Roles in the Integrated Events of Eucaryotic Gene Expression. J Biochem 141: 601–608.
112 Yoichi, S., Tatsuya, M., Tomohide, T., Shinji, K., Hiromichi, W., Teruhisa, K., Masatoshi, F., Akira, S., Toru, K., and Koji, H. 2010. Cyclin-dependent Kinase-9 Is a Component of the p300/GATA4 Complex Required for Phenylephrine-induced Hypertrophy in Cardiomyocytes. J Biol Chem 258: 9556-9568.
113 Steven H. 2004. Structure and mechanism of the RNA Polymerase II transcription machinery. Nat Struct Mol Biol 11(5): 394–403.
114 Piergiorgio, P. and Neus, V. 2006. Molecular functions of nuclear actin in transcription. J Biol Chem 172: 967-971.
115 Ivan, A. Olave, S.L., Reck-Peterson and Gerald, R. Crabtree. 2002. Nuclear actin and actin-related proteins in chromatin remodeling. Annu Rev Biochem. 71: 755-781.
116 Neus Visa. 2005. Actin in transcription. EMBO reports 6: 218-219.
117 Blaine, T. B., David, M.G., and David, C.A. 2004. Actin up in the nucleus. Natrue 5: 410-415.
118 Wu, J. and Gerald, R.C. 2007. Nuclear Actin as Choreographer of Cell Morphology and Transcription. Science 317: 1710-1711.
119 Stuven, T., Hartmann, E., G?rlich, D. 2003. Exportin 6: A novel nuclear export receptor that is specific for profilin. actin complexes. EMBO J 22: 5928–5940.
120 McDonald, D., Carrero, G., Andrin, C., de Vries, G., Hendzel, M.J. 2006. Nucleoplasmicβ-actin exists in a dynamic equilibrium between low-mobility polymeric species and rapidly diffusing populations. J Cell Biol 13: 541–552.
121 Jockusch, B.M., Schoenenberger, C.A., Stetefeld, J., Aebi, U. 2006. Tracking down the different forms of nuclear actin. Trends Cell Biol 16:391–396.
122 Wu, X., Yoo, Y., Okuhama, N.N., Tucker, P.W., Liu, G., Guan, J.L. 2006. Regulation of RNA polymerase II-dependent transcription by N-WASP and its nuclear binding partners. Nat Cell Biol 8: 756–763.
123 Yoo, Y., Wu, X., and Guan, J.L. 2007. A novel role of the actin nucleating ARP2/3 complex in the regulation of RNA polymerase II dependent transcription. J Biol Chem 282: 7616–7623.
124 Vieu E, N Hernandez. 2006. Actin’s latest act: polymerizing to facilitate transcription? Nat Cell Biol 8: 650–651.
125 Obrdlik, A., Kukalev, A., Louvet, E., Farrants, A.K., Caputo, L., Percipalle, P. 2008. The histone acetyltransferase PCAF associates with actin and hnRNP U for RNA polymerase II transcription. Mol Cell Biol 28: 6342–6357.
126 Hartzog, G.A., Speer, J.L., Lindstrom, D.L. 2002. Transcript elongation on a nucleoprotein template. Biochim Biophys Acta 1577: 276–286.