The interplay between H2A.Z and H3K9 methylation in regulating HP1α binding to linker histone-containing chromatin

Nucleic Acids Research
Daniel P Ryan, David J Tremethick

Abstract

One of the most intensively studied chromatin binding factors is HP1α. HP1α is associated with silenced, heterochromatic regions of the genome and binds to H3K9me3. While H3K9me3 is necessary for HP1α recruitment to heterochromatin, it is becoming apparent that it is not sufficient suggesting that additional factors are involved. One candidate proposed as a potential regulator of HP1α recruitment is the linker histone H1.4. Changes to the underlying make-up of chromatin, such as the incorporation of the histone variant H2A.Z, has also been linked with regulating HP1 binding to chromatin. Here, we rigorously dissected the effects of H1.4, H2A.Z and H3K9me3 on the nucleosome binding activity of HP1α in vitro employing arrays, mononucleosomes and nucleosome core particles. Unexpectedly, histone H1.4 impedes the binding of HP1α but strikingly, this inhibition is partially relieved by the incorporation of both H2A.Z and H3K9me3 but only in the context of arrays or nucleosome core particles. Our data suggests that there are two modes of interaction of HP1α with nucleosomes. The first primary mode is through interactions with linker DNA. However, when linker DNA is missing or occluded by linker histones, HP1α directly interacts with t...Continue Reading

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Citations

Jul 1, 2020·Critical Reviews in Microbiology·Zhenhui Chen, Nadia Ponts
Jul 16, 2020·Nature Reviews. Molecular Cell Biology·Sara Martire, Laura A Banaszynski
Jun 16, 2019·Epigenetics & Chromatin·Benedetto Daniele GiaimoTilman Borggrefe
Apr 9, 2020·Nucleic Acids Research·Edwige BelottiLaurent Schaeffer
Mar 8, 2020·Biophysics Reviews·Amarjeet Kumar, Hidetoshi Kono
Dec 19, 2020·Cell Proliferation·Juqing ZhangJinlian Hua
Nov 21, 2020·Current Opinion in Cell Biology·Alessandro Scacchetti, Peter B Becker
Jun 5, 2021·Biophysical Journal·Susav PradhanMartin A K Williams

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Methods Mentioned

BETA
gel filtration
PCR
electrophoretic mobility shift

Software Mentioned

MicroCal OriginPro
Jalview
ImageJ
ClustalX
smFRET

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