Linker histone H1 and H3K56 acetylation are antagonistic regulators of nucleosome dynamics

Morgan Bernier; Yi Luo; Kingsley C. Nwokelo; Michelle Goodwin; Sarah J. Dreher; Pei Zhang; Mark R. Parthun; Yvonne Fondufe-Mittendorf; Jennifer J. Ottesen; Michael G. Poirier

doi:10.1038/ncomms10152

Linker histone H1 and H3K56 acetylation are antagonistic regulators of nucleosome dynamics

Morgan Bernier, Yi Luo, Kingsley C. Nwokelo, Michelle Goodwin, Sarah J. Dreher, Pei Zhang, Mark R. Parthun, Yvonne Fondufe-Mittendorf, Jennifer J. Ottesen, Michael G. Poirier

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

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.

Original language	English
Article number	10152
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms10152
State	Published - Dec 9 2015

Bibliographical note

Funding Information:
We thank Justin North for help with nucleosome sample preparation and the initial H1.0 titrations. We thank John C. Shimko for assistance with modified histone preparation and analysis. 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.).

Funding

We thank Justin North for help with nucleosome sample preparation and the initial H1.0 titrations. We thank John C. Shimko for assistance with modified histone preparation and analysis. 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.).

Funders	Funder number
National Science Foundation (NSF)	1517986
National Institutes of Health (NIH)	R01 ES024478, R01 GM62970
National Institute of General Medical Sciences	R01GM083055

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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title = "Linker histone H1 and H3K56 acetylation are antagonistic regulators of nucleosome dynamics",

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.",

author = "Morgan Bernier and Yi Luo and Nwokelo, {Kingsley C.} and Michelle Goodwin and Dreher, {Sarah J.} and Pei Zhang and Parthun, {Mark R.} and Yvonne Fondufe-Mittendorf and Ottesen, {Jennifer J.} and Poirier, {Michael G.}",

note = "Funding Information: We thank Justin North for help with nucleosome sample preparation and the initial H1.0 titrations. We thank John C. Shimko for assistance with modified histone preparation and analysis. 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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AU - Nwokelo, Kingsley C.

AU - Goodwin, Michelle

AU - Dreher, Sarah J.

AU - Zhang, Pei

AU - Parthun, Mark R.

AU - Fondufe-Mittendorf, Yvonne

AU - Ottesen, Jennifer J.

AU - Poirier, Michael G.

N1 - Funding Information: We thank Justin North for help with nucleosome sample preparation and the initial H1.0 titrations. We thank John C. Shimko for assistance with modified histone preparation and analysis. 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.).

PY - 2015/12/9

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N2 - 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.

AB - 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.

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Linker histone H1 and H3K56 acetylation are antagonistic regulators of nucleosome dynamics

Abstract

Bibliographical note

Funding

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