title: 3D Chromosome Regulatory Landscape of Human Pluripotent Cells.
abstract: In this study, we describe the 3D chromosome regulatory landscape of human naive and primed embryonic stem cells. To devise this map, we identified transcriptional enhancers and insulators in these cells and placed them within the context of cohesin-associated CTCF-CTCF loops using cohesin ChIA-PET data. The CTCF-CTCF loops we identified form a chromosomal framework of insulated neighborhoods, which in turn form topologically associating domains (TADs) that are largely preserved during the transition between the naive and primed states. Regulatory changes in enhancer-promoter interactions occur within insulated neighborhoods during cell state transition. The CTCF anchor regions we identified are conserved across species, influence gene expression, and are a frequent site of mutations in cancer cells, underscoring their functional importance in cellular regulation. These 3D regulatory maps of human pluripotent cells therefore provide a foundation for future interrogation of the relationships between chromosome structure and gene control in development and disease.
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Xiong
authors.initials: X
authors.lastname: Ji
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Dadon
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Powell
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA; Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Zi Peng
authors.initials: ZP
authors.lastname: Fan
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Diego
authors.initials: D
authors.lastname: Borges-Rivera
authors.affiliation: National Cancer Institute (NCI), NIH, Bethesda, MD 20892, USA.
authors.forename: Sigal
authors.initials: S
authors.lastname: Shachar
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Abraham S
authors.initials: AS
authors.lastname: Weintraub
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Denes
authors.initials: D
authors.lastname: Hnisz
authors.affiliation: High Throughput Imaging Facility (HiTIF), NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Pegoraro
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Tong Ihn
authors.initials: TI
authors.lastname: Lee
authors.affiliation: National Cancer Institute (NCI), NIH, Bethesda, MD 20892, USA.
authors.forename: Tom
authors.initials: T
authors.lastname: Misteli
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: jaenisch@wi.mit.edu.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Jaenisch
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: young@wi.mit.edu.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Young
mesh_terms: D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D002877:Chromosomes, Human / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004194:Disease / Q000235:genetics; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D000066449:Human Embryonic Stem Cells / Q000378:metabolism; D006801:Humans; D038101:Insulator Elements / Q000235:genetics; D035683:MicroRNAs / Q000378:metabolism; D009690:Nucleic Acid Conformation; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D012097:Repressor Proteins; D014157:Transcription Factors / Q000378:metabolism; D000097722:Cohesins
chemical_list: D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004247:DNA; D035683:MicroRNAs; D012097:Repressor Proteins; D014157:Transcription Factors; D000097722:Cohesins; C000619697:CTCF protein, human