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

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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 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.

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Figure 1: Genome-wide binding profiles of OCT4, NANOG and CTCF reveal limited evolutionary conservation and the role of transposable elements in facilitating binding site diversity.
Figure 2: Binding sites and RABS are enriched in proximity to regulated genes.
Figure 3: Binding profiles around regulated genes reveal functional binding site turnover and the presence of RABS in proximity of human-specific targets.
Figure 4: Transposable elements have wired new genes into the core regulatory network of human embryonic stem cells.

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  • 13 June 2010

    In the version of this article initially published online, the phrase “the genes encoding” was erroneously inserted into the second sentence of the abstract and the protein name of POU5F1 was incorrect. The error has been corrected for the print, PDF and HTML versions of this article.

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Acknowledgements

This work was supported by the Agency for Science, Technology and Research (A*STAR) of Singapore.

Author information

Authors and Affiliations

Authors

Contributions

H.-H.N. and G.B. designed the experiments. N.-Y.C., X.L. and Y.-S.C. performed the experiments. G.K. performed the data analysis with contributions from J.J. and C.H. G.B. wrote the manuscript with contributions from H.-H.N. and G.K.

Corresponding author

Correspondence to Guillaume Bourque.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–7, Supplementary Tables 1–10 and Supplementary Note. (PDF 723 kb)

Supplementary Table 1

Human RABS for OCT4, NANOG and CTCF (XLS 59 kb)

Supplementary Table 2

Mouse RABS for Oct4, Nanog and Ctcf (XLS 23 kb)

Supplementary Table 3

Human and mouse POU5F1 and Pou5f1 RNAi results (XLS 492 kb)

Supplementary Table 5

OCT4 binding regions around the conserved and the human-specific OCT4 target genes (XLS 158 kb)

Supplementary Table 6

OCT4 binding regions (XLS 3530 kb)

Supplementary Table 7

NANOG binding regions (ZIP 1994 kb)

Supplementary Table 8

CTCF binding regions (ZIP 2003 kb)

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Kunarso, G., Chia, NY., Jeyakani, J. et al. Transposable elements have rewired the core regulatory network of human embryonic stem cells. Nat Genet 42, 631–634 (2010). https://doi.org/10.1038/ng.600

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