Passive and active DNA methylation and the interplay with genetic variation in gene regulation

被引：314

作者：

Gutierrez-Arcelus, Maria ^{[1
,2
,3
]}

Lappalainen, Tuuli ^{[1
,2
,3
]}

Montgomery, Stephen B. ^{[1
,4
,5
]}

Buil, Alfonso ^{[1
,2
,3
]}

Ongen, Halit ^{[1
,2
,3
]}

Yurovsky, Alisa ^{[1
,2
,3
]}

Bryois, Julien ^{[1
,2
,3
]}

Giger, Thomas ^{[1
,2
]}

Romano, Luciana ^{[1
,2
,3
]}

Planchon, Alexandra ^{[1
,2
,3
]}

Falconnet, Emilie ^{[1
,2
]}

Bielser, Deborah ^{[1
,2
]}

Gagnebin, Maryline ^{[1
,2
]}

Padioleau, Ismael ^{[1
,2
,3
]}

Borel, Christelle ^{[1
,2
]}

Letourneau, Audrey ^{[1
,2
]}

Makrythanasis, Periklis ^{[1
,2
]}

Guipponi, Michel ^{[1
,2
]}

Gehrig, Corinne ^{[1
,2
]}

Antonarakis, Stylianos E. ^{[1
,2
]}

Dermitzakis, Emmanouil T. ^{[1
,2
,3
]}

机构：

[1] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland

[2] Inst Genet & Genom Geneva, Geneva, Switzerland

[3] Swiss Inst Bioinformat, Geneva, Switzerland

[4] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA

[5] Stanford Univ, Dept Genet, Stanford, CA 94305 USA

来源：

ELIFE | 2013年 / 2卷

基金：

瑞士国家科学基金会; 欧洲研究理事会;

关键词：

EXPRESSION VARIATION; GENOME; CHROMATIN; SEQUENCE; BINDING; ANNOTATION; MECHANISMS; PROFILES; PATTERNS; ISLANDS;

D O I：

10.7554/eLife.00523

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

DNA methylation is an essential epigenetic mark whose role in gene regulation and its dependency on genomic sequence and environment are not fully understood. In this study we provide novel insights into the mechanistic relationships between genetic variation, DNA methylation and transcriptome sequencing data in three different cell-types of the GenCord human population cohort. We find that the association between DNA methylation and gene expression variation among individuals are likely due to different mechanisms from those establishing methylation-expression patterns during differentiation. Furthermore, cell-type differential DNA methylation may delineate a platform in which local inter-individual changes may respond to or act in gene regulation. We show that unlike genetic regulatory variation, DNA methylation alone does not significantly drive allele specific expression. Finally, inferred mechanistic relationships using genetic variation as well as correlations with TF abundance reveal both a passive and active role of DNA methylation to regulatory interactions influencing gene expression.

引用

页数：18

共 56 条

[1] An integrated map of genetic variation from 1,092 human genomes [J].

Altshuler, David M. ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Donnelly, Peter ;

Eichler, Evan E. ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Green, Eric D. ;

Hurles, Matthew E. ;

Knoppers, Bartha M. ;

Korbel, Jan O. ;

Lander, Eric S. ;

Lee, Charles ;

Lehrach, Hans ;

Mardis, Elaine R. ;

Marth, Gabor T. ;

McVean, Gil A. ;

Nickerson, Deborah A. ;

Schmidt, Jeanette P. ;

Sherry, Stephen T. ;

Wang, Jun ;

Wilson, Richard K. ;

Gibbs, Richard A. ;

Dinh, Huyen ;

Kovar, Christie ;

Lee, Sandra ;

Lewis, Lora ;

Muzny, Donna ;

Reid, Jeff ;

Wang, Min ;

Wang, Jun ;

Fang, Xiaodong ;

Guo, Xiaosen ;

Jian, Min ;

Jiang, Hui ;

Jin, Xin ;

Li, Guoqing ;

Li, Jingxiang ;

Li, Yingrui ;

Li, Zhuo ;

Liu, Xiao ;

Lu, Yao ;

Ma, Xuedi ;

Su, Zhe ;

Tai, Shuaishuai ;

Tang, Meifang .

NATURE, 2012, 491 (7422) :56-65

[2] Integrating common and rare genetic variation in diverse human populations [J].

Altshuler, David M. ;

Gibbs, Richard A. ;

Peltonen, Leena ;

Dermitzakis, Emmanouil ;

Schaffner, Stephen F. ;

Yu, Fuli ;

Bonnen, Penelope E. ;

de Bakker, Paul I. W. ;

Deloukas, Panos ;

Gabriel, Stacey B. ;

Gwilliam, Rhian ;

Hunt, Sarah ;

Inouye, Michael ;

Jia, Xiaoming ;

Palotie, Aarno ;

Parkin, Melissa ;

Whittaker, Pamela ;

Chang, Kyle ;

Hawes, Alicia ;

Lewis, Lora R. ;

Ren, Yanru ;

Wheeler, David ;

Muzny, Donna Marie ;

Barnes, Chris ;

Darvishi, Katayoon ;

Hurles, Matthew ;

Korn, Joshua M. ;

Kristiansson, Kati ;

Lee, Charles ;

McCarroll, Steven A. ;

Nemesh, James ;

Keinan, Alon ;

Montgomery, Stephen B. ;

Pollack, Samuela ;

Price, Alkes L. ;

Soranzo, Nicole ;

Gonzaga-Jauregui, Claudia ;

Anttila, Verneri ;

Brodeur, Wendy ;

Daly, Mark J. ;

Leslie, Stephen ;

McVean, Gil ;

Moutsianas, Loukas ;

Nguyen, Huy ;

Zhang, Qingrun ;

Ghori, Mohammed J. R. ;

McGinnis, Ralph ;

McLaren, William ;

Takeuchi, Fumihiko ;

Grossman, Sharon R. .

NATURE, 2010, 467 (7311) :52-58

[3] DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines [J].

Bell, Jordana T. ;

Pai, Athma A. ;

Pickrell, Joseph K. ;

Gaffney, Daniel J. ;

Pique-Regi, Roger ;

Degner, Jacob F. ;

Gilad, Yoav ;

Pritchard, Jonathan K. .

GENOME BIOLOGY, 2011, 12 (01)

[4] High-throughput DNA methylation profiling using universal bead arrays [J].

Bibikova, M ;

Lin, ZW ;

Zhou, LX ;

Chudin, E ;

Garcia, EW ;

Wu, B ;

Doucet, D ;

Thomas, NJ ;

Wang, YH ;

Vollmer, E ;

Goldmann, T ;

Seifart, C ;

Jiang, W ;

Barker, DL ;

Chee, MS ;

Floros, J ;

Fan, JB .

GENOME RESEARCH, 2006, 16 (03) :383-393

[5] DNA methylation patterns and epigenetic memory [J].

Bird, A .

GENES & DEVELOPMENT, 2002, 16 (01) :6-21

[6] Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project [J].

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 .

NATURE, 2007, 447 (7146) :799-816

[7] An Sp1/Sp3 Binding Polymorphism Confers Methylation Protection [J].

Boumber, Yanis A. ;

Kondo, Yutaka ;

Chen, Xuqi ;

Shen, Lanlan ;

Guo, Yi ;

Tellez, Carmen ;

Estecio, Marcos R. H. ;

Ahmed, Saira ;

Issa, Jean-Pierre J. .

PLOS GENETICS, 2008, 4 (08)

[8] High-resolution mapping and characterization of open chromatin across the genome [J].

Boyle, Alan P. ;

Davis, Sean ;

Shulha, Hennady P. ;

Meltzer, Paul ;

Margulies, Elliott H. ;

Weng, Zhiping ;

Furey, Terrence S. ;

Crawford, Gregory E. .

CELL, 2008, 132 (02) :311-322

[9] A Unified Approach to Genotype Imputation and Haplotype-Phase Inference for Large Data Sets of Trios and Unrelated Individuals [J].

Browning, Brian L. ;

Browning, Sharon R. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2009, 84 (02) :210-223

[10] Common Regulatory Variation Impacts Gene Expression in a Cell Type-Dependent Manner [J].

Dimas, Antigone S. ;

Deutsch, Samuel ;

Stranger, Barbara E. ;

Montgomery, Stephen B. ;

Borel, Christelle ;

Attar-Cohen, Homa ;

Ingle, Catherine ;

Beazley, Claude ;

Arcelus, Maria Gutierrez ;

Sekowska, Magdalena ;

Gagnebin, Marilyne ;

Nisbett, James ;

Deloukas, Panos ;

Dermitzakis, Emmanouil T. ;

Antonarakis, Stylianos E. .

SCIENCE, 2009, 325 (5945) :1246-1250

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