Oct4 dependence of chromatin structure within the extended Nanog locus in ES cells.
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.
Levasseur
Dana N
DN
Division of Hematology-Oncology, Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Harvard Stem Cell Institute, Boston, MA 02115, USA.
Wang
Jianlong
J
Dorschner
Michael O
MO
Stamatoyannopoulos
John A
JA
Orkin
Stuart H
SH
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
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