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

• Published in: Nature communications Vol. 5; no. 1; p. 5490
• Main Authors: Beck, Samuel, Lee, Bum-Kyu, Rhee, Catherine, Song, Jawon, Woo, Andrew J, Kim, Jonghwan
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 18.11.2014; Nature Pub. Group
• Subjects: Animals; Base Sequence; Cell Line; CpG Islands - genetics; DNA Methylation - genetics; DNA-Binding Proteins - classification; DNA-Binding Proteins - genetics; Embryonic Stem Cells - cytology; Enhancer Elements, Genetic - genetics; Gene Expression Regulation - genetics; Genes, Regulator; Mice; Polycomb-Group Proteins - genetics; Promoter Regions, Genetic; Proto-Oncogene Proteins c-myc - genetics; Sequence Analysis, DNA
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms6490

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.