MNase titration reveals differences between nucleosome occupancy and chromatin accessibility

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 () and Michael Y. Tolstorukov ()
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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

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms11485

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