Chd1 regulates open chromatin and pluripotency of embryonic stem cells

Alexandre Gaspar-Maia, Adi Alajem, Fanny Polesso, Rupa Sridharan, Mike J. Mason, Amy Heidersbach, João Ramalho-Santos, Michael T. McManus, Kathrin Plath, Eran Meshorer and Miguel Ramalho-Santos ()
Additional contact information
Alexandre Gaspar-Maia: 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
Adi Alajem: Institute of Life Sciences, The Hebrew University of Jerusalem
Fanny Polesso: 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
Rupa Sridharan: University of California, Los Angeles, PO Box 951737, Los Angeles, California 90095, USA
Mike J. Mason: University of California, Los Angeles, PO Box 951737, Los Angeles, California 90095, USA
Amy Heidersbach: Diabetes Center, University of California, San Francisco, California 94143-0534, USA
João Ramalho-Santos: Center for Neuroscience and Cell Biology, University of Coimbra
Michael T. McManus: Diabetes Center, University of California, San Francisco, California 94143-0534, USA
Kathrin Plath: University of California, Los Angeles, PO Box 951737, Los Angeles, California 90095, USA
Eran Meshorer: Institute of Life Sciences, The Hebrew University of Jerusalem
Miguel Ramalho-Santos: 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

Nature, 2009, vol. 460, issue 7257, 863-868

Abstract: 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.

Date: 2009
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DOI: 10.1038/nature08212

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