Histone Deacetylase-Dependent Establishment and Maintenance of Broad Low-Level Histone Acetylation within a Tissue-Specific Chromatin Domain
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- 作者：Hogune Im ; Jeffrey A. Grass ; Heather M. Christensen ; Andrew Perkins ; and Emery H. Bresnick
- 刊名：Biochemistry
- 出版年：2002
- 出版时间：December 24, 2002
- 年：2002
- 卷：41
- 期：51
- 页码：15152 - 15160
- 全文大小：205K
- 年卷期：v.41,no.51(December 24, 2002)
- ISSN：1520-4995
文摘
The murine 
-globin locus in adult erythroid cells is characterized by a broad pattern oferythroid-specific histone acetylation. The embryonic -globin genes Ey and H1 are located in a ~30kb central subdomain characterized by low-level histone acetylation, while the fetal/adult genes majorand minor and the upstream locus control region reside in hyperacetylated chromatin. Histone deacetylase(HDAC) inhibitors induce H4 acetylation at the Ey promoter [Forsberg, E. C., Downs, K. M., Christensen,H. M., Im, H., Nuzzi, P. A., and Bresnick, E. H. (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 14494-14499],indicating that HDACs maintain low-level H4 acetylation at this site. Since little is known about theestablishment of broad histone modification patterns, we asked whether this mechanism applies only tothe promoter or to the entire subdomain. We show that the HDAC inhibitor trichostatin A induces H4hyperacetylation at multiple sites within the subdomain in erythroid cells. The hematopoietic factors p45/NF-E2, GATA-1, and erythroid kruppel-like factor (EKLF), which function through cis elements of the-globin locus, were not required for induction of H4 hyperacetylation. Analysis of chromatin structurewithin the subdomain revealed low accessibility to restriction endonucleases and nearly complete CpGdinucleotide methylation. Induction of H4 hyperacetylation did not restore hallmark features oftranscriptionally active chromatin. We propose that an HDAC-dependent surveillance mechanismcounteracts constitutive histone acetyltransferase (HAT) access, thereby maintaining low-level H4acetylation throughout the subdomain.
-globin locus in adult erythroid cells is characterized by a broad pattern oferythroid-specific histone acetylation. The embryonic -globin genes Ey and H1 are located in a ~30kb central subdomain characterized by low-level histone acetylation, while the fetal/adult genes majorand minor and the upstream locus control region reside in hyperacetylated chromatin. Histone deacetylase(HDAC) inhibitors induce H4 acetylation at the Ey promoter [Forsberg, E. C., Downs, K. M., Christensen,H. M., Im, H., Nuzzi, P. A., and Bresnick, E. H. (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 14494-14499],indicating that HDACs maintain low-level H4 acetylation at this site. Since little is known about theestablishment of broad histone modification patterns, we asked whether this mechanism applies only tothe promoter or to the entire subdomain. We show that the HDAC inhibitor trichostatin A induces H4hyperacetylation at multiple sites within the subdomain in erythroid cells. The hematopoietic factors p45/NF-E2, GATA-1, and erythroid kruppel-like factor (EKLF), which function through cis elements of the-globin locus, were not required for induction of H4 hyperacetylation. Analysis of chromatin structurewithin the subdomain revealed low accessibility to restriction endonucleases and nearly complete CpGdinucleotide methylation. Induction of H4 hyperacetylation did not restore hallmark features oftranscriptionally active chromatin. We propose that an HDAC-dependent surveillance mechanismcounteracts constitutive histone acetyltransferase (HAT) access, thereby maintaining low-level H4acetylation throughout the subdomain.