title: Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes.
abstract: The pluripotent state of embryonic stem cells (ESCs) is produced by active transcription of genes that control cell identity and repression of genes encoding lineage-specifying developmental regulators. Here, we use ESC cohesin ChIA-PET data to identify the local chromosomal structures at both active and repressed genes across the genome. The results produce a map of enhancer-promoter interactions and reveal that super-enhancer-driven genes generally occur within chromosome structures that are formed by the looping of two interacting CTCF sites co-occupied by cohesin. These looped structures form insulated neighborhoods whose integrity is important for proper expression of local genes. We also find that repressed genes encoding lineage-specifying developmental regulators occur within insulated neighborhoods. These results provide insights into the relationship between transcriptional control of cell identity genes and control of local chromosome structure.
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Dowen
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142.|Computational and Systems Biology Program.
authors.forename: Zi Peng
authors.initials: ZP
authors.lastname: Fan
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142.
authors.forename: Denes
authors.initials: D
authors.lastname: Hnisz
authors.affiliation: Systems Biology Center, NHLBI, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.|College of Animal Science and Technology, Northwest A&F University, Xi'An, P. R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Ren
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Abraham
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139.
authors.forename: Lyndon N
authors.initials: LN
authors.lastname: Zhang
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139.
authors.forename: Abraham S
authors.initials: AS
authors.lastname: Weintraub
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142.
authors.forename: Jurian
authors.initials: J
authors.lastname: Schujiers
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142.
authors.forename: Tong Ihn
authors.initials: TI
authors.lastname: Lee
authors.affiliation: Systems Biology Center, NHLBI, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Keji
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Young
mesh_terms: D000818:Animals; D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D033481:Chromosomes, Mammalian / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D016678:Genome; D059014:High-Throughput Nucleotide Sequencing; D051379:Mice; D009928:Organ Specificity; D039904:Pluripotent Stem Cells / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D017422:Sequence Analysis, DNA; D000097722:Cohesins
chemical_list: D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D012097:Repressor Proteins; D000097722:Cohesins; C000619698:Ctcf protein, mouse