Chd1 regulates open chromatin and pluripotency of embryonic stem cells.
An open chromatin largely devoid of heterochromatin is a hallmark of stem cells. It remains unknown whether an open chromatin is necessary for the differentiation potential of stem cells, and which molecules are needed to maintain open chromatin. Here we show that the chromatin remodelling factor Chd1 is required to maintain the open chromatin of pluripotent mouse embryonic stem cells. Chd1 is a euchromatin protein that associates with the promoters of active genes, and downregulation of Chd1 leads to accumulation of heterochromatin. Chd1-deficient embryonic stem cells are no longer pluripotent, because they are incapable of giving rise to primitive endoderm and have a high propensity for neural differentiation. Furthermore, Chd1 is required for efficient reprogramming of fibroblasts to the pluripotent stem cell state. Our results indicate that Chd1 is essential for open chromatin and pluripotency of embryonic stem cells, and for somatic cell reprogramming to the pluripotent state.
Gaspar-Maia
Alexandre
A
Department of Ob/Gyn and Pathology, Center for Reproductive Sciences and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, California 94143-0525, USA.
Alajem
Adi
A
Polesso
Fanny
F
Sridharan
Rupa
R
Mason
Mike J
MJ
Heidersbach
Amy
A
Ramalho-Santos
João
J
McManus
Michael T
MT
Plath
Kathrin
K
Meshorer
Eran
E
Ramalho-Santos
Miguel
M
D000818:Animals; D015415:Biomarkers; D049109:Cell Proliferation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D042002:Chromatin Assembly and Disassembly; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D004707:Endoderm / Q000378:metabolism; D022041:Euchromatin / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D050993:GATA6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008745:Methylation; D051379:Mice; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference
D015415:Biomarkers; C489844:Chd1 protein, mouse; D004268:DNA-Binding Proteins; D022041:Euchromatin; D050993:GATA6 Transcription Factor; C494760:Gata6 protein, mouse; D006657:Histones; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse