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MNase titration reveals differences between nucleosome occupancy and chromatin accessibility

Author

Listed:
  • Jakub Mieczkowski

    (Massachusetts General Hospital and Harvard Medical School)

  • April Cook

    (Massachusetts General Hospital and Harvard Medical School)

  • Sarah K. Bowman

    (Massachusetts General Hospital and Harvard Medical School)

  • Britta Mueller

    (Massachusetts General Hospital and Harvard Medical School)

  • Burak H. Alver

    (Harvard Medical School)

  • Sharmistha Kundu

    (Massachusetts General Hospital and Harvard Medical School)

  • Aimee M. Deaton

    (Massachusetts General Hospital and Harvard Medical School)

  • Jennifer A. Urban

    (Cell Biology and Biochemistry, Brown University)

  • Erica Larschan

    (Cell Biology and Biochemistry, Brown University)

  • Peter J. Park

    (Harvard Medical School)

  • Robert E. Kingston

    (Massachusetts General Hospital and Harvard Medical School)

  • Michael Y. Tolstorukov

    (Massachusetts General Hospital and Harvard Medical School)

Abstract

Chromatin accessibility plays a fundamental role in gene regulation. Nucleosome placement, usually measured by quantifying protection of DNA from enzymatic digestion, can regulate accessibility. We introduce a metric that uses micrococcal nuclease (MNase) digestion in a novel manner to measure chromatin accessibility by combining information from several digests of increasing depths. This metric, MACC (MNase accessibility), quantifies the inherent heterogeneity of nucleosome accessibility in which some nucleosomes are seen preferentially at high MNase and some at low MNase. MACC interrogates each genomic locus, measuring both nucleosome location and accessibility in the same assay. MACC can be performed either with or without a histone immunoprecipitation step, and thereby compares histone and non-histone protection. We find that changes in accessibility at enhancers, promoters and other regulatory regions do not correlate with changes in nucleosome occupancy. Moreover, high nucleosome occupancy does not necessarily preclude high accessibility, which reveals novel principles of chromatin regulation.

Suggested Citation

  • Jakub Mieczkowski & April Cook & Sarah K. Bowman & Britta Mueller & Burak H. Alver & Sharmistha Kundu & Aimee M. Deaton & Jennifer A. Urban & Erica Larschan & Peter J. Park & Robert E. Kingston & Mich, 2016. "MNase titration reveals differences between nucleosome occupancy and chromatin accessibility," Nature Communications, Nature, vol. 7(1), pages 1-11, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11485
    DOI: 10.1038/ncomms11485
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    Cited by:

    1. Carlos Rivera & Hun-Goo Lee & Anna Lappala & Danni Wang & Verónica Noches & Montserrat Olivares-Costa & Marcela Sjöberg-Herrera & Jeannie T. Lee & María Estela Andrés, 2022. "Unveiling RCOR1 as a rheostat at transcriptionally permissive chromatin," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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