1. Departments 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
2. Diabetes Center, University of California, San Francisco, California 94143-0534, USA
3. PhD Programme in Biomedicine and Experimental Biology (BEB), Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal
4. Department of Genetics, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
5. Department of Biological Chemistry and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, PO Box 951737, Los Angeles, California 90095, USA
6. Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal

Correspondence to: Miguel Ramalho-Santos^1,2 Correspondence and requests for materials should be addressed to M.R.-S. (Email: mrsantos@diabetes.ucsf.edu).

Abstract

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.

1. Departments 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
2. Diabetes Center, University of California, San Francisco, California 94143-0534, USA
3. PhD Programme in Biomedicine and Experimental Biology (BEB), Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal
4. Department of Genetics, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
5. Department of Biological Chemistry and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, PO Box 951737, Los Angeles, California 90095, USA
6. Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal

Correspondence to: Miguel Ramalho-Santos^1,2 Correspondence and requests for materials should be addressed to M.R.-S. (Email: mrsantos@diabetes.ucsf.edu).

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