Linking DNA Methyltransferases to Epigenetic Marks and Nucleosome Structure Genome-wide in Human Tumor Cells

被引：87
作者：
Jin, Bilian [1 ]
Ernst, Jason [3 ,4 ]
Tiedemann, Rochelle L. [1 ]
Xu, Hongyan [1 ,2 ]
Sureshchandra, Suhas [1 ,2 ]
Kellis, Manolis [3 ,4 ]
Dalton, Stephen [5 ]
Liu, Chen [6 ]
Choi, Jeong-Hyeon [1 ,2 ]
Robertson, Keith D. [1 ]
机构：
[1] Georgia Hlth Sci Univ, Canc Res Ctr, Augusta, GA 30912 USA
[2] Georgia Hlth Sci Univ, Dept Biostat, Augusta, GA 30912 USA
[3] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA
[4] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA
[5] Univ Georgia, Paul D Coverdell Ctr Biomed & Hlth Sci, Athens, GA 30602 USA
[6] Univ Florida, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA
来源：
CELL REPORTS | 2012年 / 2卷 / 05期
基金：
美国国家科学基金会; 美国国家卫生研究院;
关键词：
EMBRYONIC STEM-CELLS; DE-NOVO METHYLATION; DNMT3B; HYPERMETHYLATION; DIFFERENTIATION; IDENTIFICATION; TRANSCRIPTION; ORGANIZATION; REPLICATION; PATTERNS;
D O I：
10.1016/j.celrep.2012.10.017
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
DNA methylation, mediated by the combined action of three DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B), is essential for mammalian development and is a major contributor to cellular transformation. To elucidate how DNA methylation is targeted, we mapped the genome-wide localization of all DNMTs and methylation, and examined the relationships among these markers, histone modifications, and nucleosome structure in a pluripotent human tumor cell line in its undifferentiated and differentiated states. Our findings reveal a strong link between DNMTs and transcribed loci, and that DNA methylation is not a simple sum of DNMT localization patterns. A comparison of the epigenomes of normal and cancerous stem cells, and pluripotent and differentiated states shows that the presence of at least two DNMTs is strongly associated with loci targeted for DNA hypermethylation. Taken together, these results shed important light on the determinants of DNA methylation and how it may become disrupted in cancer cells.
引用
收藏
页码：1411 / 1424
页数：14
相关论文
共 36 条
  • [1] LSD1 regulates the balance between self-renewal and differentiation in human embryonic stem cells
    Adamo, Antonio
    Sese, Borja
    Boue, Stephanie
    Castano, Julio
    Paramonov, Ida
    Barrero, Maria J.
    Izpisua Belmonte, Juan Carlos
    [J]. NATURE CELL BIOLOGY, 2011, 13 (06) : 652 - U265
  • [2] Replication timing-related and gene body-specific methylation of active human genes
    Aran, Dvir
    Toperoff, Gidon
    Rosenberg, Michael
    Hellman, Asaf
    [J]. HUMAN MOLECULAR GENETICS, 2011, 20 (04) : 670 - 680
  • [3] High-resolution profiling of histone methylations in the human genome
    Barski, Artern
    Cuddapah, Suresh
    Cui, Kairong
    Roh, Tae-Young
    Schones, Dustin E.
    Wang, Zhibin
    Wei, Gang
    Chepelev, Iouri
    Zhao, Keji
    [J]. CELL, 2007, 129 (04) : 823 - 837
  • [4] A decade of exploring the cancer epigenome - biological and translational implications
    Baylin, Stephen B.
    Jones, Peter A.
    [J]. NATURE REVIEWS CANCER, 2011, 11 (10) : 726 - 734
  • [5] The complex language of chromatin regulation during transcription
    Berger, Shelley L.
    [J]. NATURE, 2007, 447 (7143) : 407 - 412
  • [6] Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
    Birney, Ewan
    Stamatoyannopoulos, John A.
    Dutta, Anindya
    Guigo, Roderic
    Gingeras, Thomas R.
    Margulies, Elliott H.
    Weng, Zhiping
    Snyder, Michael
    Dermitzakis, Emmanouil T.
    Stamatoyannopoulos, John A.
    Thurman, Robert E.
    Kuehn, Michael S.
    Taylor, Christopher M.
    Neph, Shane
    Koch, Christoph M.
    Asthana, Saurabh
    Malhotra, Ankit
    Adzhubei, Ivan
    Greenbaum, Jason A.
    Andrews, Robert M.
    Flicek, Paul
    Boyle, Patrick J.
    Cao, Hua
    Carter, Nigel P.
    Clelland, Gayle K.
    Davis, Sean
    Day, Nathan
    Dhami, Pawandeep
    Dillon, Shane C.
    Dorschner, Michael O.
    Fiegler, Heike
    Giresi, Paul G.
    Goldy, Jeff
    Hawrylycz, Michael
    Haydock, Andrew
    Humbert, Richard
    James, Keith D.
    Johnson, Brett E.
    Johnson, Ericka M.
    Frum, Tristan T.
    Rosenzweig, Elizabeth R.
    Karnani, Neerja
    Lee, Kirsten
    Lefebvre, Gregory C.
    Navas, Patrick A.
    Neri, Fidencio
    Parker, Stephen C. J.
    Sabo, Peter J.
    Sandstrom, Richard
    Shafer, Anthony
    [J]. NATURE, 2007, 447 (7146) : 799 - 816
  • [7] Relationship between nucleosome positioning and DNA methylation
    Chodavarapu, Ramakrishna K.
    Feng, Suhua
    Bernatavichute, Yana V.
    Chen, Pao-Yang
    Stroud, Hume
    Yu, Yanchun
    Hetzel, Jonathan A.
    Kuo, Frank
    Kim, Jin
    Cokus, Shawn J.
    Casero, David
    Bernal, Maria
    Huijser, Peter
    Clark, Amander T.
    Kraemer, Ute
    Merchant, Sabeeha S.
    Zhang, Xiaoyu
    Jacobsen, Steven E.
    Pellegrini, Matteo
    [J]. NATURE, 2010, 466 (7304) : 388 - 392
  • [8] Identification of preferential target sites for human DNA methyltransferases
    Choi, Si Ho
    Heo, Kyu
    Byun, Hyang-Min
    An, Woojin
    Lu, Wange
    Yang, Allen S.
    [J]. NUCLEIC ACIDS RESEARCH, 2011, 39 (01) : 104 - 118
  • [9] The Dnmt3a PWWP Domain Reads Histone 3 Lysine 36 Trimethylation and Guides DNA Methylation
    Dhayalan, Arunkumar
    Rajavelu, Arumugam
    Rathert, Philipp
    Tamas, Raluca
    Jurkowska, Renata Z.
    Ragozin, Sergey
    Jeltsch, Albert
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (34) : 26114 - 26120
  • [10] Immunodeficiency, centromeric region instability, facial anomalies syndrome (ICF)
    Ehrlich, Melanie
    Jackson, Kelly
    Weemaes, Corry
    [J]. ORPHANET JOURNAL OF RARE DISEASES, 2006, 1 (1)
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