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Nucleosomal occupancy changes locally over key regulatory regions during cell differentiation and reprogramming

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  • Jason A. West

    (Massachusetts General Hospital
    Harvard Medical School
    Present address: Therapeutic Innovation Unit, Amgen, Inc., Cambridge, Massachusetts 02142, USA)

  • April Cook

    (Massachusetts General Hospital
    Harvard Medical School)

  • Burak H. Alver

    (Center for Biomedical Informatics, Harvard Medical School)

  • Matthias Stadtfeld

    (The Helen L. and Martin S. Kimmel Center for Biology and Medicine, The Skirball Institute of Biomolecular Medicine, New York University School of Medicine)

  • Aimee M. Deaton

    (Massachusetts General Hospital
    Harvard Medical School)

  • Konrad Hochedlinger

    (Howard Hughes Medical Institute and the Center for Regenerative Medicine, Massachusetts General Hospital
    Harvard University)

  • Peter J. Park

    (Center for Biomedical Informatics, Harvard Medical School)

  • Michael Y. Tolstorukov

    (Massachusetts General Hospital)

  • Robert E. Kingston

    (Massachusetts General Hospital
    Harvard Medical School)

Abstract

Chromatin structure determines DNA accessibility. We compare nucleosome occupancy in mouse and human embryonic stem cells (ESCs), induced-pluripotent stem cells (iPSCs) and differentiated cell types using MNase-seq. To address variability inherent in this technique, we developed a bioinformatic approach to identify regions of difference (RoD) in nucleosome occupancy between pluripotent and somatic cells. Surprisingly, most chromatin remains unchanged; a majority of rearrangements appear to affect a single nucleosome. RoDs are enriched at genes and regulatory elements, including enhancers associated with pluripotency and differentiation. RoDs co-localize with binding sites of key developmental regulators, including the reprogramming factors Klf4, Oct4/Sox2 and c-Myc. Nucleosomal landscapes in ESC enhancers are extensively altered, exhibiting lower nucleosome occupancy in pluripotent cells than in somatic cells. Most changes are reset during reprogramming. We conclude that changes in nucleosome occupancy are a hallmark of cell differentiation and reprogramming and likely identify regulatory regions essential for these processes.

Suggested Citation

  • Jason A. West & April Cook & Burak H. Alver & Matthias Stadtfeld & Aimee M. Deaton & Konrad Hochedlinger & Peter J. Park & Michael Y. Tolstorukov & Robert E. Kingston, 2014. "Nucleosomal occupancy changes locally over key regulatory regions during cell differentiation and reprogramming," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5719
    DOI: 10.1038/ncomms5719
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