Abstract

H1 linker histones are highly abundant proteins that compact nucleosomes and chromatin to regulate DNA accessibility and transcription. However, the mechanisms that target H1 regulation to specific regions of eukaryotic genomes are unknown. Here we report fluorescence measurements of human H1 regulation of nucleosome dynamics and transcription factor (TF) binding within nucleosomes. H1 does not block TF binding, instead it suppresses nucleosome unwrapping to reduce DNA accessibility within H1-bound nucleosomes. We then investigated H1 regulation by H3K56 and H3K122 acetylation, two transcriptional activating histone post translational modifications (PTMs). Only H3K56 acetylation, which increases nucleosome unwrapping, abolishes H1.0 reduction of TF binding. These findings show that nucleosomes remain dynamic, while H1 is bound and H1 dissociation is not required for TF binding within the nucleosome. Furthermore, our H3K56 acetylation measurements suggest that a single-histone PTM can define regions of the genome that are not regulated by H1.

Document Type

Article

Publication Date

12-9-2015

Notes/Citation Information

Published in Nature Communications, v. 6, article 10152, p. 1-10.

© 2015 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Digital Object Identifier (DOI)

http://dx.doi.org/10.1038/ncomms10152

Funding Information

This research is supported by the NIH grants R01 GM083055 (to M.G.P. and J.J.O.), R01 ES024478 (to Y.F.M.) and R01 GM62970 (to M.R.P.), and the NSF grant 1517986 (to Y.F.M.).

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Supplementary Figures 1-9 and Supplementary Table 1

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