Genetic Control of Chromatin States in Humans Involves Local and Distal Chromosomal Interactions

被引：236

作者：

Grubert, Fabian ^{[1
]}

Zaugg, Judith B. ^{[1
,2
]}

Kasowski, Maya ^{[1
]}

Ursu, Oana ^{[1
]}

Spacek, Damek V. ^{[1
]}

Martin, Alicia R. ^{[1
]}

Greenside, Peyton ^{[3
]}

Srivas, Rohith ^{[1
]}

Phanstiel, Doug H. ^{[1
]}

Pekowska, Aleksandra ^{[2
]}

Heidari, Nastaran ^{[1
]}

Euskirchen, Ghia ^{[1
]}

Huber, Wolfgang ^{[2
]}

Pritchard, Jonathan K. ^{[1
,4
,5
]}

Bustamante, Carlos D. ^{[1
]}

Steinmetz, Lars M. ^{[1
,2
]}

Kundaje, Anshul ^{[1
,6
]}

Snyder, Michael ^{[1
]}

机构：

[1] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA

[2] European Mol Biol Lab, D-69117 Heidelberg, Germany

[3] Stanford Univ, Sch Med, Biomed Informat Grad Training Program, Stanford, CA 94305 USA

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

[5] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA

[6] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA

来源：

CELL | 2015年 / 162卷 / 05期

基金：

欧洲研究理事会;

关键词：

LONG-RANGE INTERACTION; HUMAN GENOME; SUSCEPTIBILITY LOCI; ALZHEIMERS-DISEASE; CROHNS-DISEASE; HUMAN-CELLS; VARIANTS; DNA; TRANSCRIPTION; METAANALYSIS;

D O I：

10.1016/j.cell.2015.07.048

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Deciphering the impact of genetic variants on gene regulation is fundamental to understanding human disease. Although gene regulation often involves long-range interactions, it is unknown to what extent non-coding genetic variants influence distal molecular phenotypes. Here, we integrate chromatin profiling for three histone marks in lymphoblastoid cell lines (LCLs) from 75 sequenced individuals with LCL-specific Hi-C and ChIA-PET-based chromatin contact maps to uncover one of the largest collections of local and distal histone quantitative trait loci (hQTLs). Distal QTLs are enriched within topologically associated domains and exhibit largely concordant variation of chromatin state coordinated by proximal and distal non-coding genetic variants. Histone QTLs are enriched for common variants associated with autoimmune diseases and enable identification of putative target genes of disease-associated variants from genome-wide association studies. These analyses provide insights into how genetic variation can affect human disease phenotypes by coordinated changes in chromatin at interacting regulatory elements.

引用

页码：1051 / 1065

页数：15

共 39 条

[1] Independent filtering increases detection power for high-throughput experiments [J].

Bourgon, Richard ;

Gentleman, Robert ;

Huber, Wolfgang .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (21) :9546-9551

[2] DNase I sensitivity QTLs are a major determinant of human expression variation [J].

Degner, Jacob F. ;

Pai, Athma A. ;

Pique-Regi, Roger ;

Veyrieras, Jean-Baptiste ;

Gaffney, Daniel J. ;

Pickrell, Joseph K. ;

De Leon, Sherryl ;

Michelini, Katelyn ;

Lewellen, Noah ;

Crawford, Gregory E. ;

Stephens, Matthew ;

Gilad, Yoav ;

Pritchard, Jonathan K. .

NATURE, 2012, 482 (7385) :390-394

[3] Topological domains in mammalian genomes identified by analysis of chromatin interactions [J].

Dixon, Jesse R. ;

Selvaraj, Siddarth ;

Yue, Feng ;

Kim, Audrey ;

Li, Yan ;

Shen, Yin ;

Hu, Ming ;

Liu, Jun S. ;

Ren, Bing .

NATURE, 2012, 485 (7398) :376-380

[4] An integrated encyclopedia of DNA elements in the human genome [J].

Dunham, Ian ;

Kundaje, Anshul ;

Aldred, Shelley F. ;

Collins, Patrick J. ;

Davis, CarrieA. ;

Doyle, Francis ;

Epstein, Charles B. ;

Frietze, Seth ;

Harrow, Jennifer ;

Kaul, Rajinder ;

Khatun, Jainab ;

Lajoie, Bryan R. ;

Landt, Stephen G. ;

Lee, Bum-Kyu ;

Pauli, Florencia ;

Rosenbloom, Kate R. ;

Sabo, Peter ;

Safi, Alexias ;

Sanyal, Amartya ;

Shoresh, Noam ;

Simon, Jeremy M. ;

Song, Lingyun ;

Trinklein, Nathan D. ;

Altshuler, Robert C. ;

Birney, Ewan ;

Brown, James B. ;

Cheng, Chao ;

Djebali, Sarah ;

Dong, Xianjun ;

Dunham, Ian ;

Ernst, Jason ;

Furey, Terrence S. ;

Gerstein, Mark ;

Giardine, Belinda ;

Greven, Melissa ;

Hardison, Ross C. ;

Harris, Robert S. ;

Herrero, Javier ;

Hoffman, Michael M. ;

Iyer, Sowmya ;

Kellis, Manolis ;

Khatun, Jainab ;

Kheradpour, Pouya ;

Kundaje, Anshul ;

Lassmann, Timo ;

Li, Qunhua ;

Lin, Xinying ;

Marinov, Georgi K. ;

Merkel, Angelika ;

Mortazavi, Ali .

NATURE, 2012, 489 (7414) :57-74

[5] Mapping and analysis of chromatin state dynamics in nine human cell types [J].

Ernst, Jason ;

Kheradpour, Pouya ;

Mikkelsen, Tarjei S. ;

Shoresh, Noam ;

Ward, Lucas D. ;

Epstein, Charles B. ;

Zhang, Xiaolan ;

Wang, Li ;

Issner, Robbyn ;

Coyne, Michael ;

Ku, Manching ;

Durham, Timothy ;

Kellis, Manolis ;

Bernstein, Bradley E. .

NATURE, 2011, 473 (7345) :43-U52

[6] Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci [J].

Franke, Andre ;

McGovern, Dermot P. B. ;

Barrett, Jeffrey C. ;

Wang, Kai ;

Radford-Smith, Graham L. ;

Ahmad, Tariq ;

Lees, Charlie W. ;

Balschun, Tobias ;

Lee, James ;

Roberts, Rebecca ;

Anderson, Carl A. ;

Bis, Joshua C. ;

Bumpstead, Suzanne ;

Ellinghaus, David ;

Festen, Eleonora M. ;

Georges, Michel ;

Green, Todd ;

Haritunians, Talin ;

Jostins, Luke ;

Latiano, Anna ;

Mathew, Christopher G. ;

Montgomery, Grant W. ;

Prescott, Natalie J. ;

Raychaudhuri, Soumya ;

Rotter, Jerome I. ;

Schumm, Philip ;

Sharma, Yashoda ;

Simms, Lisa A. ;

Taylor, Kent D. ;

Whiteman, David ;

Wijmenga, Cisca ;

Baldassano, Robert N. ;

Barclay, Murray ;

Bayless, Theodore M. ;

Brand, Stephan ;

Buening, Carsten ;

Cohen, Albert ;

Colombel, Jean-Frederick ;

Cottone, Mario ;

Stronati, Laura ;

Denson, Ted ;

De Vos, Martine ;

D'Inca, Renata ;

Dubinsky, Marla ;

Edwards, Cathryn ;

Florin, Tim ;

Franchimont, Denis ;

Gearry, Richard ;

Glas, Juergen ;

Van Gossum, Andre .

NATURE GENETICS, 2010, 42 (12) :1118-+

[7] An oestrogen-receptor-α-bound human chromatin interactome [J].

Fullwood, Melissa J. ;

Liu, Mei Hui ;

Pan, You Fu ;

Liu, Jun ;

Xu, Han ;

Bin Mohamed, Yusoff ;

Orlov, Yuriy L. ;

Velkov, Stoyan ;

Ho, Andrea ;

Mei, Poh Huay ;

Chew, Elaine G. Y. ;

Huang, Phillips Yao Hui ;

Welboren, Willem-Jan ;

Han, Yuyuan ;

Ooi, Hong Sain ;

Ariyaratne, Pramila N. ;

Vega, Vinsensius B. ;

Luo, Yanquan ;

Tan, Peck Yean ;

Choy, Pei Ye ;

Wansa, K. D. Senali Abayratna ;

Zhao, Bing ;

Lim, Kar Sian ;

Leow, Shi Chi ;

Yow, Jit Sin ;

Joseph, Roy ;

Li, Haixia ;

Desai, Kartiki V. ;

Thomsen, Jane S. ;

Lee, Yew Kok ;

Karuturi, R. Krishna Murthy ;

Herve, Thoreau ;

Bourque, Guillaume ;

Stunnenberg, Hendrik G. ;

Ruan, Xiaoan ;

Cacheux-Rataboul, Valere ;

Sung, Wing-Kin ;

Liu, Edison T. ;

Wei, Chia-Lin ;

Cheung, Edwin ;

Ruan, Yijun .

NATURE, 2009, 462 (7269) :58-64

[8] Conserved epigenomic signals in mice and humans reveal immune basis of Alzheimer's disease [J].

Gjoneska, Elizabeta ;

Pfenning, Andreas R. ;

Mathys, Hansruedi ;

Quon, Gerald ;

Kundaje, Anshul ;

Tsai, Li-Huei ;

Kellis, Manolis .

NATURE, 2015, 518 (7539) :365-369

[9] 9p21 DNA variants associated with coronary artery disease impair interferon-γ signalling response [J].

Harismendy, Olivier ;

Notani, Dimple ;

Song, Xiaoyuan ;

Rahim, Nazli G. ;

Tanasa, Bogdan ;

Heintzman, Nathaniel ;

Ren, Bing ;

Fu, Xiang-Dong ;

Topol, Eric J. ;

Rosenfeld, Michael G. ;

Frazer, Kelly A. .

NATURE, 2011, 470 (7333) :264-+

[10] GENCODE: The reference human genome annotation for The ENCODE Project [J].

Harrow, Jennifer ;

Frankish, Adam ;

Gonzalez, Jose M. ;

Tapanari, Electra ;

Diekhans, Mark ;

Kokocinski, Felix ;

Aken, Bronwen L. ;

Barrell, Daniel ;

Zadissa, Amonida ;

Searle, Stephen ;

Barnes, If ;

Bignell, Alexandra ;

Boychenko, Veronika ;

Hunt, Toby ;

Kay, Mike ;

Mukherjee, Gaurab ;

Rajan, Jeena ;

Despacio-Reyes, Gloria ;

Saunders, Gary ;

Steward, Charles ;

Harte, Rachel ;

Lin, Michael ;

Howald, Cedric ;

Tanzer, Andrea ;

Derrien, Thomas ;

Chrast, Jacqueline ;

Walters, Nathalie ;

Balasubramanian, Suganthi ;

Pei, Baikang ;

Tress, Michael ;

Manuel Rodriguez, Jose ;

Ezkurdia, Iakes ;

van Baren, Jeltje ;

Brent, Michael ;

Haussler, David ;

Kellis, Manolis ;

Valencia, Alfonso ;

Reymond, Alexandre ;

Gerstein, Mark ;

Guigo, Roderic ;

Hubbard, Tim J. .

GENOME RESEARCH, 2012, 22 (09) :1760-1774

← 1 2 3 4 →