Transposable elements have rewired the core regulatory network of human embryonic stem cells

被引：569

作者：

Kunarso, Galih ^{[2
]}

Chia, Na-Yu ^{[1
,3
]}

Jeyakani, Justin

Hwang, Catalina ^{[4
]}

Lu, Xinyi ^{[1
,5
]}

Chan, Yun-Shen ^{[1
,6
]}

Ng, Huck-Hui ^{[1
,3
,5
,6
,7
]}

Bourque, Guillaume ^{[1
]}

机构：

[1] Genome Inst Singapore, Gene Regulat Lab, Singapore, Singapore

[2] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore

[3] Nanyang Technol Univ, Sch Biol Sci, Singapore, Singapore

[4] Princeton Univ, Princeton, NJ 08544 USA

[5] Natl Univ Singapore, Dept Biol Sci, Singapore 117548, Singapore

[6] Natl Univ Singapore, Grad Sch Integrat Sci & Engn, Singapore 117548, Singapore

[7] Natl Univ Singapore, Dept Biochem, Singapore 117548, Singapore

来源：

NATURE GENETICS | 2010年 / 42卷 / 07期

关键词：

FACTOR-BINDING SITES; HUMAN GENOME; TRANSCRIPTIONAL NETWORK; GENE-EXPRESSION; PROTEIN CTCF; EVOLUTION; VERTEBRATE; MOUSE; LINES;

D O I：

10.1038/ng.600

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Detection of new genomic control elements is critical in understanding transcriptional regulatory networks in their entirety. We studied the genome-wide binding locations of three key regulatory proteins (POU5F1, also known as OCT4; NANOG; and CTCF) in human and mouse embryonic stem cells. In contrast to CTCF, we found that the binding profiles of OCT4 and NANOG are markedly different, with only similar to 5% of the regions being homologously occupied. We show that transposable elements contributed up to 25% of the bound sites in humans and mice and have wired new genes into the core regulatory network of embryonic stem cells. These data indicate that species-specific transposable elements have substantially altered the transcriptional circuitry of pluripotent stem cells.

引用

页码：631 / U111

页数：5

共 29 条

[1] The protein CTCF is required for the enhancer blocking activity of vertebrate insulators [J].

Bell, AC ;

West, AG ;

Felsenfeld, G .

CELL, 1999, 98 (03) :387-396

[2] 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

[3] Divergence of transcription factor binding sites across related yeast species [J].

Borneman, Anthony R. ;

Gianoulis, Tara A. ;

Zhang, Zhengdong D. ;

Yu, Haiyuan ;

Rozowsky, Joel ;

Seringhaus, Michael R. ;

Wang, Lu Yong ;

Gerstein, Mark ;

Snyder, Michael .

SCIENCE, 2007, 317 (5839) :815-819

[4] Evolution of the mammalian transcription factor binding repertoire via transposable elements [J].

Bourque, Guillaume ;

Leong, Bernard ;

Vega, Vinsensius B. ;

Chen, Xi ;

Lee, Yen Ling ;

Srinivasan, Kandhadayar G. ;

Chew, Joon-Lin ;

Ruan, Yijun ;

Wei, Chia-Lin ;

Ng, Huck Hui ;

Liu, Edison T. .

GENOME RESEARCH, 2008, 18 (11) :1752-1762

[5] Core transcriptional regulatory circuitry in human embryonic stem cells [J].

Boyer, LA ;

Lee, TI ;

Cole, MF ;

Johnstone, SE ;

Levine, SS ;

Zucker, JR ;

Guenther, MG ;

Kumar, RM ;

Murray, HL ;

Jenner, RG ;

Gifford, DK ;

Melton, DA ;

Jaenisch, R ;

Young, RA .

CELL, 2005, 122 (06) :947-956

[6] Derivation of pluripotent epiblast stem cells from mammalian embryos [J].

Brons, I. Gabrielle M. ;

Smithers, Lucy E. ;

Trotter, Matthew W. B. ;

Rugg-Gunn, Peter ;

Sun, Bowen ;

de Sousa Lopes, Susana M. Chuva ;

Howlett, Sarah K. ;

Clarkson, Amanda ;

Ahrlund-Richter, Lars ;

Pedersen, Roger A. ;

Vallier, Ludovic .

NATURE, 2007, 448 (7150) :191-U7

[7] RETROPOSONS - SEEDS OF EVOLUTION [J].

BROSIUS, J .

SCIENCE, 1991, 251 (4995) :753-753

[8] SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex [J].

Cao, R ;

Zhang, Y .

MOLECULAR CELL, 2004, 15 (01) :57-67

[9] Integration of external signaling pathways with the core transcriptional network in embryonic stem cells [J].

Chen, Xi ;

Xu, Han ;

Yuan, Ping ;

Fang, Fang ;

Huss, Mikael ;

Vega, Vinsensius B. ;

Wong, Eleanor ;

Orlov, Yuriy L. ;

Zhang, Weiwei ;

Jiang, Jianming ;

Loh, Yuin-Han ;

Yeo, Hock Chuan ;

Yeo, Zhen Xuan ;

Narang, Vipin ;

Govindarajan, Kunde Ramamoorthy ;

Leong, Bernard ;

Shahab, Atif ;

Ruan, Yijun ;

Bourque, Guillaume ;

Sung, Wing-Kin ;

Clarke, Neil D. ;

Wei, Chia-Lin ;

Ng, Huck-Hui .

CELL, 2008, 133 (06) :1106-1117

[10] Endogenous retroviral LTRs as promoters for human genes: A critical assessment [J].

Cohen, Carla J. ;

Lock, Wynne M. ;

Mager, Dixie L. .

GENE, 2009, 448 (02) :105-114

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