title: Nucleosomal occupancy changes locally over key regulatory regions during cell differentiation and reprogramming.
abstract: Chromatin structure determines DNA accessibility. We compare nucleosome occupancy in mouse and human embryonic stem cells (ESCs), induced-pluripotent stem cells (iPSCs) and differentiated cell types using MNase-seq. To address variability inherent in this technique, we developed a bioinformatic approach to identify regions of difference (RoD) in nucleosome occupancy between pluripotent and somatic cells. Surprisingly, most chromatin remains unchanged; a majority of rearrangements appear to affect a single nucleosome. RoDs are enriched at genes and regulatory elements, including enhancers associated with pluripotency and differentiation. RoDs co-localize with binding sites of key developmental regulators, including the reprogramming factors Klf4, Oct4/Sox2 and c-Myc. Nucleosomal landscapes in ESC enhancers are extensively altered, exhibiting lower nucleosome occupancy in pluripotent cells than in somatic cells. Most changes are reset during reprogramming. We conclude that changes in nucleosome occupancy are a hallmark of cell differentiation and reprogramming and likely identify regulatory regions essential for these processes.
authors.affiliation: 1] Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA [3] [4].
authors.forename: Jason A
authors.initials: JA
authors.lastname: West
authors.affiliation: 1] Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA [3].
authors.forename: April
authors.initials: A
authors.lastname: Cook
authors.affiliation: Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Burak H
authors.initials: BH
authors.lastname: Alver
authors.affiliation: The Helen L. and Martin S. Kimmel Center for Biology and Medicine, The Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Stadtfeld
authors.affiliation: 1] Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Aimee M
authors.initials: AM
authors.lastname: Deaton
authors.affiliation: 1] Howard Hughes Medical Institute and the Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA [2] The Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Konrad
authors.initials: K
authors.lastname: Hochedlinger
authors.affiliation: Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Park
authors.affiliation: 1] Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA [2].
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Tolstorukov
authors.affiliation: 1] Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Kingston
mesh_terms: D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000502:physiology*; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D000090062:Kruppel-Like Factor 4; D051379:Mice; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D024363:Transcription Initiation Site
chemical_list: D002843:Chromatin; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D009707:Nucleosomes; D014157:Transcription Factors