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Chd1 regulates open chromatin and pluripotency of embryonic stem cells

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  • 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
    Diabetes Center, University of California, San Francisco, California 94143-0534, USA
    PhD Programme in Biomedicine and Experimental Biology (BEB), Center for Neuroscience and Cell Biology, University of Coimbra)

  • 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
    Diabetes Center, University of California, San Francisco, California 94143-0534, 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
    Diabetes Center, University of California, San Francisco, California 94143-0534, USA)

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.

Suggested Citation

  • Alexandre Gaspar-Maia & Adi Alajem & Fanny Polesso & Rupa Sridharan & Mike J. Mason & Amy Heidersbach & João Ramalho-Santos & Michael T. McManus & Kathrin Plath & Eran Meshorer & Miguel Ramalho-Santos, 2009. "Chd1 regulates open chromatin and pluripotency of embryonic stem cells," Nature, Nature, vol. 460(7257), pages 863-868, August.
    • Handle: RePEc:nat:nature:v:460:y:2009:i:7257:d:10.1038_nature08212
    DOI: 10.1038/nature08212
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    Cited by:

    1. Mei Sheng Lau & Zhenhua Hu & Xiaodan Zhao & Yaw Sing Tan & Jinyue Liu & Hua Huang & Clarisse Jingyi Yeo & Hwei Fen Leong & Oleg V. Grinchuk & Justin Kaixuan Chan & Jie Yan & Wee-Wei Tee, 2023. "Transcriptional repression by a secondary DNA binding surface of DNA topoisomerase I safeguards against hypertranscription," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Florian Lienert & Fabio Mohn & Vijay K Tiwari & Tuncay Baubec & Tim C Roloff & Dimos Gaidatzis & Michael B Stadler & Dirk Schübeler, 2011. "Genomic Prevalence of Heterochromatic H3K9me2 and Transcription Do Not Discriminate Pluripotent from Terminally Differentiated Cells," PLOS Genetics, Public Library of Science, vol. 7(6), pages 1-9, June.

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