Enhancer regions show high histone H3.3 turnover that changes during differentiation

  1. Aimee M Deaton
  2. Mariluz Gómez-Rodríguez
  3. Jakub Mieczkowski
  4. Michael Y Tolstorukov
  5. Sharmistha Kundu
  6. Ruslan I Sadreyev
  7. Lars ET Jansen
  8. Robert E Kingston  Is a corresponding author
  1. Massachusetts General Hospital, United States
  2. Instituto Gulbenkian de Ciencia, Portugal
  3. Instituto Gulbenkian de Ciência, Portugal

Abstract

The organization of DNA into chromatin is dynamic; nucleosomes are frequently displaced to facilitate the ability of regulatory proteins to access specific DNA elements. To gain insight into nucleosome dynamics, and to follow how dynamics change during differentiation, we used a technique called time-ChIP to quantitatively assess histone H3.3 turnover genome-wide during differentiation of mouse ESCs. We found that, without prior assumptions, high turnover could be used to identify regions involved in gene regulation. High turnover was seen at enhancers, as observed previously, with particularly high turnover at super-enhancers. In contrast, regions associated with the repressive Polycomb-Group showed low turnover in ESCs. Turnover correlated with DNA accessibility. Upon differentiation, numerous changes in H3.3 turnover rates were observed, the majority of which occurred at enhancers. Thus, time-ChIP measurement of histone turnover shows that active enhancers are unusually dynamic in ESCs and changes in highly dynamic nucleosomes predominate at enhancers during differentiation.

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Author details

  1. Aimee M Deaton

    Department of Molecular Biology, Massachusetts General Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Mariluz Gómez-Rodríguez

    Laboratory for Epigenetic Mechanisms, Instituto Gulbenkian de Ciencia, Oeiras, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  3. Jakub Mieczkowski

    Department of Molecular Biology, Massachusetts General Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Michael Y Tolstorukov

    Department of Molecular Biology, Massachusetts General Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Sharmistha Kundu

    Department of Molecular Biology, Massachusetts General Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Ruslan I Sadreyev

    Department of Molecular Biology, Massachusetts General Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Lars ET Jansen

    Laboratory for Epigenetic Mechanisms, Instituto Gulbenkian de Ciência, Oeiras, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  8. Robert E Kingston

    Department of Molecular Biology, Massachusetts General Hospital, Boston, United States
    For correspondence
    kingston@molbio.mgh.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.

Copyright

© 2016, Deaton et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Aimee M Deaton
  2. Mariluz Gómez-Rodríguez
  3. Jakub Mieczkowski
  4. Michael Y Tolstorukov
  5. Sharmistha Kundu
  6. Ruslan I Sadreyev
  7. Lars ET Jansen
  8. Robert E Kingston
(2016)
Enhancer regions show high histone H3.3 turnover that changes during differentiation
eLife 5:e15316.
https://doi.org/10.7554/eLife.15316

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https://doi.org/10.7554/eLife.15316