CpG island-mediated global gene regulatory modes in mouse embryonic stem cells

Samuel Beck, Bum-Kyu Lee, Catherine Rhee, Jawon Song, Andrew J. Woo and Jonghwan Kim ()
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Samuel Beck: The University of Texas at Austin
Bum-Kyu Lee: The University of Texas at Austin
Catherine Rhee: The University of Texas at Austin
Jawon Song: Texas Advanced Computing Center, The University of Texas at Austin
Andrew J. Woo: School of Medicine and Pharmacology, Royal Perth Hospital Unit, The University of Western Australia
Jonghwan Kim: The University of Texas at Austin

Nature Communications, 2014, vol. 5, issue 1, 1-12

Abstract: Abstract Both transcriptional and epigenetic regulations are fundamental for the control of eukaryotic gene expression. Here we perform a compendium analysis of >200 large sequencing data sets to elucidate the regulatory logic of global gene expression programs in mouse embryonic stem (ES) cells. We define four major classes of DNA-binding proteins (Core, PRC, MYC and CTCF) based on their target co-occupancy, and discover reciprocal regulation between the MYC and PRC classes for the activity of nearly all genes under the control of the CpG island (CGI)-containing promoters. This CGI-dependent regulatory mode explains the functional segregation between CGI-containing and CGI-less genes during early development. By defining active enhancers based on the co-occupancy of the Core class, we further demonstrate their additive roles in CGI-containing gene expression and cell type-specific roles in CGI-less gene expression. Altogether, our analyses provide novel insights into previously unknown CGI-dependent global gene regulatory modes.

Date: 2014
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DOI: 10.1038/ncomms6490

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