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PMID: 20526341 Published · ppublish English Journal Article

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

Nature genetics ·Vol. 42 ·No. 7 ·2010-07-00 ·Pages 631-4

Kunarso G, Chia NY, Jeyakani J, Hwang C, Lu X, Chan YS, Ng HH, Bourque G

Abstract

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 approximately 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.

MeSH Terms
Animals Binding Sites/genetics CCCTC-Binding Factor DNA Transposable Elements/genetics Embryonic Stem Cells/metabolism Gene Expression Profiling Gene Regulatory Networks Genome-Wide Association Study Homeodomain Proteins/genetics,metabolism Humans Mice Models, Genetic Nanog Homeobox Protein Octamer Transcription Factor-3/genetics,metabolism Protein Binding RNA Interference Regulatory Sequences, Nucleic Acid/genetics Repressor Proteins/genetics,metabolism Species Specificity
Chemicals
CCCTC-Binding Factor CTCF protein, human Ctcf protein, mouse DNA Transposable Elements Homeodomain Proteins NANOG protein, human Nanog Homeobox Protein Nanog protein, mouse Octamer Transcription Factor-3 POU5F1 protein, human Pou5f1 protein, mouse Repressor Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Kunarso Galih
Computational and Mathematical Biology, Genome Institute of Singapore, Singapore, Singapore.
Chia Na-Yu
Jeyakani Justin
Hwang Catalina
Lu Xinyi
Chan Yun-Shen
Ng Huck-Hui
Bourque Guillaume
References (29)
29 references, click to expand
  1. Evolution of transcription factor binding sites in Mammalian gene regulatory regions: conservation and turnover.
    Mol Biol Evol. 2002 Jul;19(7):1114-21 PMID: 12082130
  2. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project.
    Nature. 2007 Jun 14;447(7146):799-816 PMID: 17571346
  3. Embryonic stem cell lines derived from human blastocysts.
    Science. 1998 Nov 6;282(5391):1145-7 PMID: 9804556
  4. Core transcriptional regulatory circuitry in human embryonic stem cells.
    Cell. 2005 Sep 23;122(6):947-56 PMID: 16153702
  5. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes.
    Genome Res. 2005 Aug;15(8):1034-50 PMID: 16024819
  6. Transposable elements and the evolution of regulatory networks.
    Nat Rev Genet. 2008 May;9(5):397-405 PMID: 18368054
  7. New cell lines from mouse epiblast share defining features with human embryonic stem cells.
    Nature. 2007 Jul 12;448(7150):196-9 PMID: 17597760
  8. Stem cells and early lineage development.
    Cell. 2008 Feb 22;132(4):527-31 PMID: 18295568
  9. Retroposons--seeds of evolution.
    Science. 1991 Feb 15;251(4995):753 PMID: 1990437
  10. Analysis of the vertebrate insulator protein CTCF-binding sites in the human genome.
    Cell. 2007 Mar 23;128(6):1231-45 PMID: 17382889
  11. The significance of responses of the genome to challenge.
    Science. 1984 Nov 16;226(4676):792-801 PMID: 15739260
  12. The protein CTCF is required for the enhancer blocking activity of vertebrate insulators.
    Cell. 1999 Aug 6;98(3):387-96 PMID: 10458613
  13. Regulation of gene expression: possible role of repetitive sequences.
    Science. 1979 Jun 8;204(4397):1052-9 PMID: 451548
  14. Derivation of pluripotent epiblast stem cells from mammalian embryos.
    Nature. 2007 Jul 12;448(7150):191-5 PMID: 17597762
  15. Divergence of transcription factor binding sites across related yeast species.
    Science. 2007 Aug 10;317(5839):815-9 PMID: 17690298
  16. Feeder-free growth of undifferentiated human embryonic stem cells.
    Nat Biotechnol. 2001 Oct;19(10):971-4 PMID: 11581665
  17. Evolution of the mammalian transcription factor binding repertoire via transposable elements.
    Genome Res. 2008 Nov;18(11):1752-62 PMID: 18682548
  18. Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53.
    Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18613-8 PMID: 18003932
  19. SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex.
    Mol Cell. 2004 Jul 2;15(1):57-67 PMID: 15225548
  20. Tissue-specific transcriptional regulation has diverged significantly between human and mouse.
    Nat Genet. 2007 Jun;39(6):730-2 PMID: 17529977
  21. Model-based analysis of ChIP-Seq (MACS).
    Genome Biol. 2008;9(9):R137 PMID: 18798982
  22. The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells.
    Nat Genet. 2006 Apr;38(4):431-40 PMID: 16518401
  23. The human genome browser at UCSC.
    Genome Res. 2002 Jun;12(6):996-1006 PMID: 12045153
  24. Endogenous retroviral LTRs as promoters for human genes: a critical assessment.
    Gene. 2009 Dec 15;448(2):105-14 PMID: 19577618
  25. Integration of external signaling pathways with the core transcriptional network in embryonic stem cells.
    Cell. 2008 Jun 13;133(6):1106-17 PMID: 18555785
  26. Large-scale turnover of functional transcription factor binding sites in Drosophila.
    PLoS Comput Biol. 2006 Oct;2(10):e130 PMID: 17040121
  27. Integrating regulatory motif discovery and genome-wide expression analysis.
    Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3339-44 PMID: 12626739
  28. Significance analysis of microarrays applied to the ionizing radiation response.
    Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21 PMID: 11309499
  29. Gene expression patterns in human embryonic stem cells and human pluripotent germ cell tumors.
    Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13350-5 PMID: 14595015
Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
Published
2010-07-00
Epub
2010-00-06
Pages
631-4
Language
English
Region
United States
NLM ID
9216904
Subset
IM
Databases
GEO
Analysis Services
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