Human Heterochromatin Protein 1α Promotes Nucleosome Associations That Drive Chromatin Condensation

Abdelhamid M Azzaz; Michael W Vitalini; Andrew S Thomas; Jason P Price; Melissa J Blacketer; Diane E Cryderman; Luka N Zirbel; Christopher L Woodcock; Adrian H Elcock; Lori L Wallrath; Michael A Shogren-Knaak

doi:10.1074/jbc.M113.512137

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Human Heterochromatin Protein 1α Promotes Nucleosome Associations That Drive Chromatin Condensation

Journal article

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Human Heterochromatin Protein 1α Promotes Nucleosome Associations That Drive Chromatin Condensation

Abdelhamid M Azzaz, Michael W Vitalini, Andrew S Thomas, Jason P Price, Melissa J Blacketer, Diane E Cryderman, Luka N Zirbel, Christopher L Woodcock, Adrian H Elcock, Lori L Wallrath, …

The Journal of biological chemistry, Vol.289(10), pp.6850-6861

03/07/2014

DOI: 10.1074/jbc.M113.512137

PMCID: PMC3945347

PMID: 24415761

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Abstract

HP1Hsα-containing heterochromatin is located near centric regions of chromosomes and regulates DNA-mediated processes such as DNA repair and transcription. The higher-order structure of heterochromatin contributes to this regulation, yet the structure of heterochromatin is not well understood. We took a multidisciplinary approach to determine how HP1Hsα-nucleosome interactions contribute to the structure of heterochromatin. We show that HP1Hsα preferentially binds histone H3K9Me3-containing nucleosomal arrays in favor of non-methylated nucleosomal arrays and that nonspecific DNA interactions and pre-existing chromatin compaction promote binding. The chromo and chromo shadow domains of HP1Hsα play an essential role in HP1Hsα-nucleosome interactions, whereas the hinge region appears to have a less significant role. Electron microscopy of HP1Hsα-associated nucleosomal arrays showed that HP1Hsα caused nucleosome associations within an array, facilitating chromatin condensation. Differential sedimentation of HP1Hsα-associated nucleosomal arrays showed that HP1Hsα promotes interactions between arrays. These strand-to-strand interactions are supported by in vivo studies where tethering the Drosophila homologue HP1a to specific sites promotes interactions with distant chromosomal sites. Our findings demonstrate that HP1Hsα-nucleosome interactions cause chromatin condensation, a process that regulates many chromosome events.

DNA and Chromosomes

Heterochromatin

DNA Binding Protein

Histone Modification

Chromatin Structure

Chromosomes

Details

Title: Subtitle: Human Heterochromatin Protein 1α Promotes Nucleosome Associations That Drive Chromatin Condensation
Creators: Abdelhamid M Azzaz - Iowa State University
Michael W Vitalini - University of Iowa
Andrew S Thomas - University of Iowa
Jason P Price - University of Iowa
Melissa J Blacketer - Iowa State University
Diane E Cryderman - University of Iowa
Luka N Zirbel - University of Iowa
Christopher L Woodcock - University of Massachusetts Amherst
Adrian H Elcock - University of Iowa
Lori L Wallrath - University of Iowa
Michael A Shogren-Knaak - Iowa State University
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.289(10), pp.6850-6861
DOI: 10.1074/jbc.M113.512137
PMID: 24415761
PMCID: PMC3945347
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
Grant note: GM061513; GM79663-03S1 / National Institutes of Health
Alternative title: HP1Hsα Promotes Nucleosome-nucleosome Associations
Language: English
Date published: 03/07/2014
Academic Unit: Physics and Astronomy; Biochemistry and Molecular Biology; University College Courses
Record Identifier: 9984024523102771

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