title: Oct4 dependence of chromatin structure within the extended Nanog locus in ES cells.
abstract: Embryonic stem (ES) cells offer insight into early developmental fate decisions, and their controlled differentiation may yield vast regenerative potential. The molecular determinants supporting ES cell self-renewal are incompletely understood. The homeodomain proteins Nanog and Oct4 are essential for mouse ES cell self-renewal. Using a high-throughput approach, we discovered DNaseI hypersensitive sites and potential regulatory elements along a 160-kb region of the genome that includes GDF3, Dppa3, and Nanog. We analyzed gene expression, chromatin occupancy, and higher-order chromatin structure throughout this gene locus and found that expression of the reprogramming factor Oct4 is required to maintain its integrity.
authors.affiliation: Division of Hematology-Oncology, Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Harvard Stem Cell Institute, Boston, MA 02115, USA.
authors.forename: Dana N
authors.initials: DN
authors.lastname: Levasseur
authors.forename: Jianlong
authors.initials: J
authors.lastname: Wang
authors.forename: Michael O
authors.initials: MO
authors.lastname: Dorschner
authors.forename: John A
authors.initials: JA
authors.lastname: Stamatoyannopoulos
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Orkin
mesh_terms: D000818:Animals; D000076246:CCCTC-Binding Factor; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000737:chemistry; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D055451:Growth Differentiation Factor 3; D018398:Homeodomain Proteins / Q000235:genetics*; D038101:Insulator Elements; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D051379:Mice; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000076246:CCCTC-Binding Factor; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; C000619698:Ctcf protein, mouse; D004268:DNA-Binding Proteins; C462180:Dppa3 protein, mouse; C525975:Gdf3 protein, mouse; D055451:Growth Differentiation Factor 3; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D003850:Deoxyribonuclease I