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

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 the nucleosome core and this interaction is enhanced by H2A.Z with H3K9me3.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Ryan DP,Tremethick DJ

doi

10.1093/nar/gky632

subject

Has Abstract

pub_date

2018-10-12 00:00:00

pages

9353-9366

issue

18

eissn

0305-1048

issn

1362-4962

pii

5051838

journal_volume

46

pub_type

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