Whole-genome bisulfite sequencing of multiple individuals reveals complementary roles of promoter and gene body methylation in transcriptional regulation
详细信息 查看全文
- 作者：Shaoke Lou (1) (2)
Heung-Man Lee (3) (4) (5)
Hao Qin (2)
Jing-Woei Li (2)
Zhibo Gao (6)
Xin Liu (6)
Landon L Chan (1) (2)
Vincent KL Lam (3) (4) (5)
Wing-Yee So (3) (4) (5)
Ying Wang (3) (4) (5)
Si Lok (7)
Jun Wang (10) (6) (8) (9)
Ronald CW Ma (3) (4) (5)
Stephen Kwok-Wing Tsui (11) (12) (13)
Juliana CN Chan (3) (4) (5)
Ting-Fung Chan (12) (13) (2)
Kevin Y Yip (1) (12) (13) (4)
1. Department of Computer Science and Engineering ; The Chinese University of Hong Kong ; Shatin ; New Territories ; Hong Kong
2. School of Life Sciences ; The Chinese University of Hong Kong ; Shatin ; New Territories ; Hong Kong
3. Department of Medicine and Therapeutics ; The Chinese University of Hong Kong ; Shatin ; New Territories ; Hong Kong
4. Hong Kong Institute of Diabetes and Obesity ; The Chinese University of Hong Kong ; Shatin ; New Territories ; Hong Kong
5. Li Ka Shing Institute of Health Sciences ; The Chinese University of Hong Kong ; Shatin ; New Territories ; Hong Kong
6. Beijing Genomics Institute (BGI)-Shenzhen ; Shenzhen ; China
7. Department of Chemical Pathology ; The Chinese University of Hong Kong ; Shatin ; New Territories ; Hong Kong
10. King Abdulaziz University ; Jeddah ; Saudi Arabia
8. Department of Biology ; University of Copenhagen ; Copenhagen ; Denmark
9. The Novo Nordisk Foundation Center for Basic Metabolic Research ; University of Copenhagen ; Copenhagen ; Denmark
11. School of Biomedical Sciences ; The Chinese University of Hong Kong ; Shatin ; New Territories ; Hong Kong
12. Hong Kong Bioinformatics Centre ; The Chinese University of Hong Kong ; Shatin ; New Territories ; Hong Kong
13. CUHK-BGI Innovation Institute of Trans-omics ; The Chinese University of Hong Kong ; Shatin ; New Territories ; Hong Kong - 刊名：Genome Biology
- 出版年：2014
- 出版时间：July 2014
- 年：2014
- 卷：15
- 期：7
- 全文大小：3,784 KB
- 参考文献：1. Bird, A (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16: pp. 6-21 CrossRef
2. Cokus, SJ, Feng, S, Zhang, X, Chen, Z, Merriman, B, Haudenschild, CD, Pradhan, S, Nelson, SF, Pellegrini, M, Jacobsen, SE (2008) Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning. Nature 452: pp. 215-219 CrossRef
3. Lister, R, O鈥橫alley, RC, Tonti-Filippini, J, Gregory, BD, Berry, CC, Millar, AH, Ecker, JR (2008) Highly integrated single-base resolution maps of the epigenome in Arabidopsis. Cell 133: pp. 523-536 CrossRef
4. Lister, R, Pelizzola, M, Dowen, RH, Hawkins, RD, Hon, G, Tonti-Filippini, J, Nery, JR, Lee, L, Ye, Z, Ngo, Q, Edsall, L, Antosiewicz-Bourget, J, Stewart, R, Ruotti, V, Millar, AH, Thomson, JA, Ren, B, Ecker, JR (2009) Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462: pp. 315-322 CrossRef
5. Ehrlich, M, Gama-Sosa, MA, Huang, LH, Midgett, RM, Kuo, KC, McCune, RA, Gehrke, C (1982) Amount and distribution of 5-methylcytosine in human DNA from different types of tissues of cells. Nucleic Acids Res 10: pp. 2709-2721 CrossRef
6. Bird, AP (1986) CpG-rich islands and the function of DNA methylation. Nature 321: pp. 209-213 CrossRef
7. Miranda, TB, Jones, PA (2007) DNA methylation: the nuts and bolts of repression. J Cell Physiol 213: pp. 384-390 CrossRef
8. Suzuki, MM, Bird, A (2008) DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet 9: pp. 465-476 CrossRef
9. Kass, SU, Pruss, D, Wolffe, AP (1977) How does DNA methylation repress transcription. Trends Genet 13: pp. 444-449 CrossRef
10. Robertson, KD (2005) DNA methylation and human disease. Nat Rev Genet 6: pp. 597-610 CrossRef
11. Portela, A, Esteller, M (2010) Epigenetic modifications and human disease. Nat Biotechnol 28: pp. 1057-1068 CrossRef
12. Beck, S, Rakyan, VK (2008) The methylome: approaches for global DNA methylation profiling. Trends Genet 24: pp. 231-237 CrossRef
13. Laird, PW (2010) Principles and challenges of genomewide DNA methylation analysis. Nat Rev Genet 11: pp. 191-203 CrossRef
14. Jones, PA (2012) Functions of DNA methylation: islands start sites gene bodies and beyond. Nat Rev Genet 13: pp. 484-492 CrossRef
15. Lippman, Z, Gendrel, A-V, Colot, V, Martienssen, R (2005) Profiling DNA methylation patterns using genomic tiling microarrays. Nat Methods 2: pp. 219-224 CrossRef
16. Khulan, B, Thompson, RF, Ye, K, Fazzari, MJ, Suzuki, M, Stasiek, E, Figueroa, ME, Glass, JL, Chen, Q, Montagna, C, Hatchwell, E, Selzer, RR, Richmond, T, Green, RD, Melnick, A, Greally, J (2006) Comparative isoschizomer profiling of cytosine methylation: the HELP assay. Genome Res 16: pp. 1046-1055 CrossRef
17. Weber, M, Davies, JJ, Wittig, D, Oakeley, EJ, Haase, M, Lam, WL, Sch眉beler, D (2005) Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nat Genet 37: pp. 853-862 CrossRef
18. Zhang, X, Yazaki, J, Sundaresan, A, Cokus, S, Chan, S. W-L, Chen, H, Henderson, IR, Shinn, P, Pellegrini, M, Jacobsen, SE (2006) Genome-wide high-resolution mapping and functional analysis of DNA methylation in Arabidopsis. Cell 126: pp. 1189-1201 CrossRef
19. Weber, M, Hellmann, I, Stadler, MB, Ramos, L, P盲盲bo, S, Rebhan, M, Sch眉beler, D (2007) Distribution silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat Genet 39: pp. 457-466 CrossRef
20. Illingworth, R, Kerr, A, Desousa, D, J酶rgensen, H, Ellis, P, Stalker, J, Jackson, D, Clee, C, Plumb, R, Rogers, J, Humphray, S, Cox, T, Langford, C, Bird, A (2008) A novel CpG island set identifies tissue-specific methylation at developmental gene loci. PLoS Biol 6: pp. e22 CrossRef
21. Brinkman, AB, Simmer, F, Ma, K, Kaan, A, Zhu, J, Stunnenberg, HG (2010) Whole-genome DNA methylation profiling using MethyCap-seq. Methods 52: pp. 232-236 CrossRef
22. Li, Y, Zhu, J, Tian, G, Li, N, Li, Q, Ye, M, Zheng, H, Yu, J, Wu, H, Sun, J, Zhang, H, Chen, Q, Luo, R, Chen, M, He, Y, Jin, X, Zhang, Q, Yu, C, Zhou, G, Sun, J, Huang, Y, Zheng, H, Cao, H, Zhou, X, Guo, S, Hu, X, Li, X, Kristiansen, K, Bolund, L, Xu, J (2010) The DNA methylome of human peripheral blood mononuclear cells. PLoS Biol 8: pp. e1.000533 CrossRef
23. Bock, C, Tomazou, EM, Brinkman, AB, M眉ller, F, Simmer, F, Gu, H, J盲ger, N, Gnirke, A, Stunnenberg, HG, Meissner, A (2010) Quantitative comparison of genome-wide DNA methylation mapping technologies. Nat Biotechnol 28: pp. 1106-1114 CrossRef
24. Harris, RA, Wang, T, Coarfa, C, Nagarajan, RP, Hong, C, Downey, SL, Johnson, BE, Fouse, SD, Delaney, A, Zhao, Y, Olshen, A, Ballinger, T, Zhou, X, Forsberg, KJ, Gu, J, Echipare, L, O鈥橤een, H, Lister, R, Pelizzola, M, Xi, Y, Epstein, CB, Bernstein, BE, Hawkins, RD, Ren, B, Chung, WY, Gu, H, Bock, C, Gnirke, A, Zhang, MQ, Haussler, D (2010) Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications. Nat Biotechnol 28: pp. 1097-1105 CrossRef
25. Bell, JT, Pai, AA, Pickrell, JK, Gaffney, DJ, Pique-Regi, R, Degner, JF, Gilad, Y, Pritchard, JK (2011) DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines. Genome Biol 12: pp. R10 CrossRef
26. Pai, AA, Bell, JT, Marioni, JC, Pritchard, JK, Gilad, Y (2011) A genome-wide study of DNA methylation patterns and gene expression levels in multiple human and chimpanzee tissues. PLoS Genet 7: pp. e1001316 CrossRef
27. Hellman, A, Chess, A (2007) Gene body-specific methylation on the active X chromosome. Science 315: pp. 1141-1143 CrossRef
28. Ball, MP, Li, JB, Gao, Y, Lee, JH, LeProust, EM, Park, IH, Xie, B, Daley, GQ, Church, GM (2009) Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells. Nat Biotechnol 27: pp. 361-368 CrossRef
29. Rauch, TA, Wu, X, Zhong, X, Riggs, AD, Pfeifer, GP (2009) A human B cell methylome at 100-base pair resolution. Proc Natl Acad Sci U S A 106: pp. 671-678 CrossRef
30. Rountree, MR, Selker, EU (1997) DNA methylation inhibits elongation but not initiation of transcription in Neurospora crassa. Genes Dev 11: pp. 2383-2395 CrossRef
31. Lorincz, MC, Dickerson, DR, Schmitt, M, Groudine, M (2004) Intragenic DNA methylation alters chromatin structure and elongation efficiency in mammalian cells. Nat Struct Mol Biol 11: pp. 1068-1075 CrossRef
32. Maunakea, AK, Nagarajan, RP, Bilenky, M, Ballinger, TJ, D鈥橲ouza, C, Fouse, SD, Johnson, BE, Hong, C, Nielsen, C, Zhao, Y, Turecki, G, Delaney, A, Varhol, R, Thiessen, N, Shchors, K, Heine, VM, Rowitch, DH, Xing, X, Fiore, C, Schillebeeckx, M, Jones, SJM, Haussler, D, Marra, MA, Hirst, M, Wang, T, Costello, JF (2010) Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature 466: pp. 253-257 CrossRef
33. Choi, JK, Bae, J-B, Lyu, J, Kim, T-Y, Kim, Y-J (2009) Nucleosome deposition and DNA methylation at coding region boundaries. Genome Biol 10: pp. R89 CrossRef
34. Cedar, H, Bergman, Y (2009) Linking DNA methylation and histone modification: patterns and paradigms. Nat Rev Genet 10: pp. 295-304 CrossRef
35. Wu, H, Coskun, V, Tao, J, Xie, W, Ge, W, Yoshikawa, K, Li, E, Zhang, Y, Sun, YE (2010) Dnmt3a-dependent nonpromoter DNA methylation facilitates transcription of neurogenic genes. Science 329: pp. 444-448 CrossRef
36. Hahn, MA, Wu, X, Li, AX, Hahn, T, Pfeifer, GP (2011) Relationship between gene body DNA methylation and intragenic H3K9me3 and H3K36me3 chromatin marks. PLoS One 6: pp. e18844 CrossRef
37. Irizarry, RA, Ladd-Acosta, C, Wen, B, Wu, Z, Montano, C, Onyango, P, Cui, H, Gabo, K, Rongione, M, Webster, M, Hong, J, James, BP, Sarven, S, Andrew, PF (2009) The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet 41: pp. 178-186 CrossRef
38. Akalin, A, Garrett-Bakelman, FE, Kormaksson, M, Busuttil, J, Zhang, L, Khrebtukova, I, Milne, TA, Huang, Y, Biswas, D, Hess, JL, Allis, CD, Roeder, RG, Valk, PJM, L枚wenberg, B, Delwel, R, Fernandez, HF, Paietta, E, Tallman, MS, Schroth, GP, Mason, CE, Melnick, A, Figueroa, ME (2012) Base-pair resolution DNA methylation sequencing reveals profoundly divergent epigenetic landscapes in acute myeloid leukemia. PLoS Genet 8: pp. e1002781 CrossRef
39. Toperoff, G, Aran, D, Kark, JD, Rosenberg, M, Dubnikov, T, Nissan, B, Wainstein, J, Friedlander, Y, Levy-Lahad, E, Glaser, B, Hellman, A (2012) Genome-wide survey reveals predisposing diabetes type 2-related DNA methylation variations in human peripheral blood. Hum Mol Genet 21: pp. 371-383 CrossRef
40. Ng, CW, Yildirim, F, Yap, YS, Dalin, S, Matthews, BJ, Velez, PJ, Labadorf, A, Housman, DE, Fraenkel, E (2013) Extensive changes in DNA methylation are associated with expression of mutant huntingtin. Proc Natl Acad Sci U S A 110: pp. 2354-2359 CrossRef
41. Huang, DW, Sherman, BT, Lempicki, RA (2008) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4: pp. 44-57 CrossRef
42. McMullan, CJ, Schernhammer, ES, Rimm, EB, Hu, FB, Forman, JP (2013) Melatonin secretion and the incidence of type 2 diabetes. JAMA 309: pp. 1388-1396 CrossRef
43. Breiman, L (2001) Random forests. Mach Learn 45: pp. 5-32 CrossRef
44. Brenet, F, Moh, M, Funk, P, Feierstein, E, Viale, AJ, Socci, ND, Scandura, JM (2011) Dna methylation of the first exon is tightly linked to transcriptional silencing. PLOS ONE 6: pp. e14524 CrossRef
45. Bernstein, BE, Stamatoyannopoulos, JA, Costello, JF, Ren, B, Milosavljevic, A, Meissner, A, Kellis, M, Marra, MA, Beaudet, AL, Ecker, JR, Farnham, PJ, Hirst, M, Lander, ES, Mikkelsen, TS, Thomson, JA () The NIH roadmap epigenomics mapping consortium. Nat Biotechnol 28: pp. 1045-1048 CrossRef
46. Cheng, C, Yan, K-K, Yip, KY, Rozowsky, J, Alexander, R, Shou, C, Gerstein, M (2011) A statistical framework for modeling gene expression using chromatin features with application to modENCODE datasets. Genome Biol 12: pp. R12 CrossRef
47. Cheng, C, Alexander, R, Min, R, Leng, J, Yip, KY, Rozowsky, J, kiu Yan, K, Dong, X, Djebali, S, Ruan, Y, Davis, CA, Carninci, P, Lassman, T, Gingeras, TR, Serra, RG, Birney, E, Weng, Z, Snyder, M, Gerstein, M (2012) Understanding transcriptional regulation by integrative analysis of transcription factor binding data. Genome Res 22: pp. 1658-1667 CrossRef
48. Zhou, VW, Goren, A, Bernstein, BE (2011) Charting histone modifications and the functional organization of mammalian genomes. Nat Rev Genet 12: pp. 7-18 CrossRef
49. Hohn, T, Corsten, S, Rieke, S, M眉ller, M, Rothnie, H (1996) Methylation of coding region alone inhibits gene expression in plant protoplasts. Proc Natl Acad Sci U S A 93: pp. 8334-8339 CrossRef
50. Li, X, Wang, X, He, K, Ma, Y, Su, N, He, H, Stolc, V, Tongprasit, W, Jin, W, Jiang, J, Terzaghi, W, Li, S, Deng, XW (2008) High-resolution mapping of epigenetic modifications of the rice genome uncovers interplay between DNA methylation histone methylation and gene expression. Plant Cell 25: pp. 259-276 CrossRef
51. Flanagan, JM, Wild, L (2007) An epigenetic role for noncoding RNAs and intragenic DNA methylation. Genome Biol 8: pp. 307 CrossRef
52. Cokus, SJ, Feng, S, Zhang, X, Chen, Z, Merriman, B, Haudenschild, CD, Pradhan, S, Nelson, SF, Pellegrini, M, Jacobsen, SE (2008) Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning. Nature 452: pp. 215-219 CrossRef
53. Djebali, S, Davis, CA, Merkel, A, Dobin, A, Lassmann, T, Mortazavi, A, Tanzer, A, Lagarde, J, Lin, W, Schlesinger, F, Xue, C, Marinov, GK, Khatun, J, Williams, BA, Zaleski, C, Rozowsky, J, R枚der, M, Kokocinski, F, Abdelhamid, RF, Alioto, T, Antoshechkin, I, Baer, MT, Bar, NS, Batut, P, Bell, K, Bell, I, Chakrabortty, S, Chen, X, Chrast, J, Curado, J (2012) Landscape of transcription in human cells. Nature 489: pp. 101-108 CrossRef
54. Aran, D, Sabato, S, Hellman, A (2013) DNA methylation of distal regulatory sites characterizes dysregulation of cancer genes. Genome Biol 14: pp. R21 CrossRef
55. Hayatsu, H, Shiraishi, M, Negishi, K (2008) Bisulfite modification for analysis of DNA methylation. Curr Protoc Nucleic Acid Chem 33: pp. 6.10.1-6.10.15
56. Li, R, Yu, C, Li, Y, Lam, T-W, Yiu, S-M, Kristiansen, K, Wang, J (2009) SOAP2: an improved ultrafast tool for short read alignment. Bioinformatics 25: pp. 1966-1967 CrossRef
57. Kent, WJ, Sugnet, CW, Furey, TS, Roskin, KM, Pringle, TH, Zahler, AM (2002) The human genome browser at UCSC. Genome Res 12: pp. 996-1006 CrossRef
58. Li, H, Durbin, R (2009) Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25: pp. 1754-1760 CrossRef
59. Trapnell, C, Pachter, L, Salzberg, SL (2009) TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25: pp. 1105-1111 CrossRef
60. Mortazavi, A, Williams, BA, McCue, K, Schaeffer, L, Wold, B (2008) Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nature Methods 5: pp. 621-628 CrossRef
61. Robinson, JT, Thorvaldsdottir, H, Winckler, W, Guttman, M, Lander, ES, Getz, G, Mesirov, JP (2011) Integrative genomics viewer. Nat Biotechnol 29: pp. 24-26 CrossRef
62. Krzywinski, MI, Schein, JE, Birol, I, Connors, J, Gascoyne, R, Horsman, D, Jones, SJ, Marra, MA (2009) Circos: an information aesthetic for comparative genomics. Genome Res 19: pp. 1639-1645 CrossRef
63. Benjamini, Y, Hochberg, Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Stat Soc Ser B 57: pp. 289-300
64. Harrow, J, Frankish, A, Gonzalez, JM, Tapanari, E, Diekhans, M, Kokocinski, F, Aken, BL, Barrell, D, Zadissa, A, Searle, S, Barnes, I, Bignell, A, Boychenko, V, Hunt, T, Kay, M, Mukherjee, G, Rajan, J, Despacio-Reyes, G, Saunders, G, Steward, C, Harte, R, Lin, M, Howald, C, Tanzer, A, Derrien, T, Chrast, J, Walters, N, Balasubramanian, S, Pei, B, Tress, M (2012) GENCODE: the reference human genome annotation for the ENCODE project. Genome Res 22: pp. 1760-1774 CrossRef
65. Hall, M, Frank, E, Holmes, G, Pfahringer, B, Reutemann, P, Witten, IH (2009) The WEKA data mining software: an update. SIGKDD Explorations 11: pp. 10-18 CrossRef
66. Edgar, R, Domrchev, M, Lash, AE (2002) Gene expression omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res 30: pp. 207-210 CrossRef - 刊物主题：Animal Genetics and Genomics; Human Genetics; Plant Genetics & Genomics; Microbial Genetics and Genomics; Fungus Genetics; Bioinformatics;
- 出版者：BioMed Central
- ISSN：1465-6906
文摘
Background DNA methylation is an important type of epigenetic modification involved in gene regulation. Although strong DNA methylation at promoters is widely recognized to be associated with transcriptional repression, many aspects of DNA methylation remain not fully understood, including the quantitative relationships between DNA methylation and expression levels, and the individual roles of promoter and gene body methylation. Results Here we present an integrated analysis of whole-genome bisulfite sequencing and RNA sequencing data from human samples and cell lines. We find that while promoter methylation inversely correlates with gene expression as generally observed, the repressive effect is clear only on genes with a very high DNA methylation level. By means of statistical modeling, we find that DNA methylation is indicative of the expression class of a gene in general, but gene body methylation is a better indicator than promoter methylation. These findings are general in that a model constructed from a sample or cell line could accurately fit the unseen data from another. We further find that promoter and gene body methylation have minimal redundancy, and either one is sufficient to signify low expression. Finally, we obtain increased modeling power by integrating histone modification data with the DNA methylation data, showing that neither type of information fully subsumes the other. Conclusion Our results suggest that DNA methylation outside promoters also plays critical roles in gene regulation. Future studies on gene regulatory mechanisms and disease-associated differential methylation should pay more attention to DNA methylation at gene bodies and other non-promoter regions.