title: CpG island-mediated global gene regulatory modes in mouse embryonic stem cells.
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.
authors.affiliation: Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas 78712, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Beck
authors.affiliation: Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas 78712, USA.
authors.forename: Bum-Kyu
authors.initials: BK
authors.lastname: Lee
authors.affiliation: Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas 78712, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Rhee
authors.affiliation: Texas Advanced Computing Center, The University of Texas at Austin, Austin, Texas 78758, USA.
authors.forename: Jawon
authors.initials: J
authors.lastname: Song
authors.affiliation: School of Medicine and Pharmacology, Royal Perth Hospital Unit, The University of Western Australia, Perth, WA 6000, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Woo
authors.affiliation: 1] Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas 78712, USA [2] Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas 78712, USA [3] Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, Texas 78712, USA.
authors.forename: Jonghwan
authors.initials: J
authors.lastname: Kim
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000145:classification / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000166:cytology*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D005809:Genes, Regulator; D051379:Mice; D063146:Polycomb-Group Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D004268:DNA-Binding Proteins; C489428:Myc protein, mouse; D063146:Polycomb-Group Proteins; D016271:Proto-Oncogene Proteins c-myc