›› 2010, Vol. 25 ›› Issue (1): 35-41.

• Special Issue on Computational Challenges from Modern Molecular Biology • Previous Articles     Next Articles

Genome-Wide Analysis of Epigenetic Modifications

Shoudan Liang (梁守丹)   

  1. Department of Bioinformatics and Computational Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, U.S.A.
  • Received:2009-10-07 Revised:2009-10-21 Online:2010-01-05 Published:2010-01-05
  • About author:
    Shoudan Liang is a professor of bioinformatics and computational biology at the University of Texas M. D. Anderson Cancer Center. He received his Ph.D. degree in physics from the University of Chicago in 1986. His research includes building tools to analyze chIP-seq experiments and DNA methylation in cancer.
  • Supported by:

    This work is supported by US NIH/NCI under Grant No. 5 K25CA123344-02.

In plants and animals, gene expression can be altered by changes that do not alter the sequence of nucleotides in DNA but rather modify the chemical structure of either the DNA or the histones that interact with the DNA. These so-called epigenetic modifications are not transient, but persist through cell divisions. Rapidly advancing technologies, such as next-generation DNA sequencing, have dramatically increased our ability to survey epigenetic markers throughout an entire genome. These techniques are revealing in great detail that the many forms and stages of cancer are characterized by a massive number of epigenetic changes. Interpreting such epigenetic marks in cell differentiation and in carcinogenesis is computationally challenging. We review several examples of epigenetic data analysis and discuss the need for computational methods that will enable us to learn from the data the relationships between different kinds of histone modifications and DNA methylation.

[1] Taverna S D, Li H, Ruthenburg A J, Allis C D, Patel D J. How chromatin-binding modules interpret histone modifications: Lessons from professional pocket pickers. Nat. Struct. Mol. Biol., 2007, 14(11): 1025-1040.
[2] Barski A, Cuddapah S, Cui K, Roh T Y, Schones D E, Wang Z, Wei G, Chepelev I, Zhao K. High-resolution profiling of histone methylations in the human genome. Cell, 2007, 129(4): 823-837.
[3] Wang Z, Zang C, Rosenfeld J A, Schones D E, Barski A, Cuddapah S, Cui K, Roh T Y, Peng W, Zhang MQ, Zhao K. Combinatorial patterns of histone acetylations and methylations in the human genome. Nat. Genet., 2008, 40(7): 897-903.
[4] Chesnokov I N, Schmid C W. Specific Alu binding protein from human sperm chromatin prevents DNA methylation. J. Biol. Chem., 1995, 270(31): 18539-18542.
[5] Vaquerizas J M, Kummerfeld S K, Teichmann S A, Luscombe N M. A census of human transcription factors: Function, expression and evolution. Nature Rev. Genet., 2009, 10(4): 252-263.
[6] Guelen L, Pagie L, Brasset E, Meuleman W, Faza M B, Talhout W, Eussen B H, de Klein A, Wessels L, de Laat W, van Steensel B. Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature, 2008, 453(7197): 948-951.
[7] Lee T I, Rinaldi N J, Robert F, Odom D T, Bar-Joseph Z, Gerber G K, Hannett N M, Harbison C T, Thompson C M, Simon I, Zeitlinger J, Jennings E G, Murray H L, Gordon D B, Ren B, Wyrick J J, Tagne J B, Volkert T L, Fraenkel E, Gifford D K, Young R A. Transcriptional regulatory networks in Saccharomyces cerevisiae. Science, 2002, 298(5594): 799-804.
[8] Harbison C T, Gordon D B, Lee T I, Rinaldi N J, Macisaac K D, Danford T W, Hannett N M, Tagne J B, Reynolds D B, Yoo J, Jennings E G, Zeitlinger J, Pokholok D K, Kellis M, Rolfe P A, Takusagawa K T, Lander E S, Gifford D K, Fraenkel E, Young R A. Transcriptional regulatory code of a eukaryotic genome. Nature, 2004, 431(7004): 99-104.
[9] Birney E, Stamatoyannopoulos J A, Dutta A et al. Identification and analysis of functional elements in 1% of the human genome by the encode pilot project. Nature, 2007, 447(7146): 799-816.
[10] Jones P A, Takai D. The role of DNA methylation in mammalian epigenetics. Science, 2001, 293(5532): 1068-1070.
[11] Bird A. DNA methylation patterns and epigenetic memory. Genes Dev., 2002, 16(1): 6-21.
[12] Razin A, Cedar H. DNA methylation and gene expression. Microbiol. Rev., 1991, 55(3): 451-458.
[13] Kass S U, Pruss D, Wolffe A P. How does DNA methylation repress transcription? Trends Genet., 1997, 13(11): 444-449.
[14] Weber M, Davies J J, Wittig D, Oakeley E J, Haase M, Lam W L, Schubeler D. Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nat. Genet., 2005, 37(8): 853-862.
[15] Eckhardt F, Lewin J, Cortese R et al. DNAmethylation profiling of human chromosomes 6, 20 and 22. Nat. Genet., 2006, 38(12): 1378-1385.
[16] Lander E S, Linton L W, Birren B et al. Initial sequencing and analysis of the human genome. Nature, 2001, 409(6822): 860-921.
[17] Cooper D N, Taggart M H, Bird A P. Unmethylated domains in vertebrate DNA. Nucleic Acids Res., 1983, 11(3): 647-658.
[18] Bird A, Taggart M, Frommer M, Miller O J, Macleod D. A fraction of the mouse genome that is derived from islands of nonmethylated, CpG-rich DNA. Cell, 1985, 40(1): 91-99.
[19] Gardiner-Garden M, Frommer M. CpG islands in vertebrate genomes. J. Mol. Biol., 1987, 196(2): 261-282.
[20] Takai D, Jones P A. Comprehensive analysis of CpG islands in human chromosomes 21 and 22. Proc. Natl. Acad. Sci. USA, 2002, 99(6): 3740-3745.
[21] Saxonov S, Berg P, Brutlag D L. A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc. Natl. Acad. Sci. USA, 2006, 103(5): 1412-1417.
[22] Roth S Y, Denu J M, Allis C D. Histone acetyltransferases. Annu. Rev. Biochem., 2001, 70: 81-120.
[23] Berger S L. An embarrassment of niches: The many covalent modifications of histones in transcriptional regulation. Oncogene, 2001, 20(24): 3007-3013.
[24] Jenuwein T, Allis C D. Translating the histone code. Science, 2001, 293(5532): 1074-1080.
[25] Lehrmann H, Pritchard L L, Harel-Bellan A. Histone acetyltransferases and deacetylases in the control of cell proliferation and differentiation. Adv. Cancer Res., 2002, 86: 41-65.
[26] Armstrong S A, Golub T R, Korsmeyer S J. Mll-rearranged leukemias: Insights from gene expression profiling. Semin Hematol, 2003, 40(4): 268-273.
[27] Issa J P. DNA methylation as a therapeutic target in cancer. Clin. Cancer Res., 2007, 13(6): 1634-1637.
[28] Lister R, Pelizzola M, Dowen R H, Hawkins R D, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo Q M, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar A H, Thomson J A, Ren B, Ecker J R. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature, 2009, 462(7271): 315-322.
[29] Zilberman D, Henikoff S. Genome-wide analysis of DNA methylation patterns. Development, 2007, 134(22):3959-3965.
[30] Zhang Y, Liu T, Meyer C A, Eeckhoute J, Johnson D S, Bernstein B E, Nussbaum C, Myers R M, Brown M, Li W, Liu X.S Model-based analysis of chIP-seq (MACS). Genome. Biol., 2008, 9(9): R137.
[31] Ji H, Jiang H, Ma W, Johnson D S, Myers R M, Wong W H. An integrated software system for analyzing chIP-chip and chIP-seq data. Nat. Biotechnol., 2008, 26(11): 1293-1300.
[32] Rozowsky J, Euskirchen G, Auerbach R K, Zhang Z D, Gibson T, Bjornson R, Carriero N, Snyder M, Gerstein M B. PeakSeq enables systematic scoring of ChIP-seq experiments relative to controls. Nat. Biotechnol., 2009, 27(1): 66-75.
[33] Frohman M A, Dush M K, Martin G R. Rapid production of full-length cDNAs from rare transcripts: Amplification using a single gene-specific oligonucleotide primer. Proc. Natl. Acad. Sci. USA, 1988, 85(23): 8998-9002.
[34] Heintzman N D, Stuart R K, Hon G, Fu Y, Ching C W, Hawkins R D, Barrera L O, Van Calcar S, Qu C, Ching K A, Wang W, Weng Z, Green R D, Crawford G E, Ren B. Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat. Genet., 2007, 39(3): 311-318.
[35] Heintzman N D, Hon G C, Hawkins R D, Kheradpour P, Stark A, Harp L F, Ye Z, Lee L K, Stuart R K, Ching C W, Ching K A, Antosiewicz-Bourget J E, Liu H, Zhang X, Green R D, Lobanenkov V V, Stewart R, Thomson J A, Crawford G E, Kellis M, Ren B. Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature, 2009, 459(7243): 108-112.
[36] Visel A, Blow M J, Li Z, Zhang T, Akiyama J A, Holt A, Plajzer-Frick I, Shoukry M, Wright C, Chen F, Afzal V, Ren B, Rubin E M, Pennacchio L A. ChIP-seq accurately predicts tissue-specific activity of enhancers. Nature, 2009, 457(7231): 854-858.
[37] Yu H, Zhu S, Zhou B, Xue H, Han J D. Inferring causal relationships among different histone modifications and gene expression. Genome Res., 2008, 18(8): 1314-1324.
[38] Goll M G, Bestor T H. Eukaryotic cytosine methyltransferases. Annu. Rev. Biochem., 2005, 74: 481-514.
[39] Wigler M, Levy D, Perucho M. The somatic replication of DNA methylation. Cell, 1981, 24(1): 33-40.
[40] Dodd IB, Micheelsen MA, Sneppen K, Thon G. Theoretical analysis of epigenetic cell memory by nucleosome modification. Cell, May 18, 2007, 129(4): 813-822.
[41] Liang J, Qian H. Computational cellular dynamics based on the chemical master equation: A challenge for understanding complexity. J. Comput. Sci. & Technol., 2010, 25(1): 154-168.
[42] Irizarry R A, Ladd-Acosta C, Carvalho B, Wu H, Brandenburg S A, Jeddeloh J A,Wen B, Feinberg A P. Comprehensive high-throughput arrays for relative methylation (CHARM). Genome. Res., 2008, 18(5): 780–790.
[43] Irizarry R A, Ladd-Acosta C, Wen B, Wu Z, Montano C, Onyango P, Cui H, Gabo K, Rongione M, Webster M, Ji H, Potash J B, Sabunciyan S, Feinberg A P. The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat. Genet., 2009, 41(2): 178-186.
[44] Doi A, Park IH, Wen B, Murakami P, Aryee MJ, Irizarry R, Herb B, Ladd-Acosta C, Rho J, Loewer S, Miller J, Schlaeger T, Daley GQ, Feinberg AP. Differential methylation of tissueand cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts. Nat. Genet., Nov. 1, 2009, PubMed PMID: 19881528. (Epub ahead of print)
[45] Widschwendter M, Fiegl H, Egle D, Mueller-Holzner E, Spizzo G, Marth C, Weisenberger D J, Campan M, Young J, Jacobs I, Laird P W. Epigenetic stem cell signature in cancer. Nat. Genet., 2007, 39(2): 157-158.
[46] Schlesinger Y, Straussman R, Keshet I, Farkash S, Hecht M, Zimmerman J, Eden E, Yakhini Z, Ben-Shushan E, Reubinoff B E, Bergman Y, Simon I, Cedar H. Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Nat. Genet., 2007, 39(2): 232- 236.

No related articles found!
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] Liu Mingye; Hong Enyu;. Some Covering Problems and Their Solutions in Automatic Logic Synthesis Systems[J]. , 1986, 1(2): 83 -92 .
[2] Chen Shihua;. On the Structure of (Weak) Inverses of an (Weakly) Invertible Finite Automaton[J]. , 1986, 1(3): 92 -100 .
[3] Gao Qingshi; Zhang Xiang; Yang Shufan; Chen Shuqing;. Vector Computer 757[J]. , 1986, 1(3): 1 -14 .
[4] Chen Zhaoxiong; Gao Qingshi;. A Substitution Based Model for the Implementation of PROLOG——The Design and Implementation of LPROLOG[J]. , 1986, 1(4): 17 -26 .
[5] Huang Heyan;. A Parallel Implementation Model of HPARLOG[J]. , 1986, 1(4): 27 -38 .
[6] Min Yinghua; Han Zhide;. A Built-in Test Pattern Generator[J]. , 1986, 1(4): 62 -74 .
[7] Tang Tonggao; Zhao Zhaokeng;. Stack Method in Program Semantics[J]. , 1987, 2(1): 51 -63 .
[8] Min Yinghua;. Easy Test Generation PLAs[J]. , 1987, 2(1): 72 -80 .
[9] Zhu Hong;. Some Mathematical Properties of the Functional Programming Language FP[J]. , 1987, 2(3): 202 -216 .
[10] Li Minghui;. CAD System of Microprogrammed Digital Systems[J]. , 1987, 2(3): 226 -235 .

ISSN 1000-9000(Print)

         1860-4749(Online)
CN 11-2296/TP

Home
Editorial Board
Author Guidelines
Subscription
Journal of Computer Science and Technology
Institute of Computing Technology, Chinese Academy of Sciences
P.O. Box 2704, Beijing 100190 P.R. China
Tel.:86-10-62610746
E-mail: jcst@ict.ac.cn
 
  Copyright ©2015 JCST, All Rights Reserved