CENP-B creates alternative epigenetic chromatin states permissive for CENP-A or heterochromatin assembly.

Abstract:

:CENP-B binds to CENP-B boxes on centromeric satellite DNAs (known as alphoid DNA in humans). CENP-B maintains kinetochore function through interactions with CENP-A nucleosomes and CENP-C. CENP-B binding to transfected alphoid DNA can induce de novo CENP-A assembly, functional centromere and kinetochore formation, and subsequent human artificial chromosome (HAC) formation. Furthermore, CENP-B also facilitates H3K9 (histone H3 lysine 9) trimethylation on alphoid DNA, mediated by Suv39h1, at ectopic alphoid DNA integration sites. Excessive heterochromatin invasion into centromere chromatin suppresses CENP-A assembly. It is unclear how CENP-B controls such different chromatin states. Here, we show that the CENP-B acidic domain recruits histone chaperones and many chromatin modifiers, including the H3K36 methylase ASH1L, as well as the heterochromatin components Suv39h1 and HP1 (HP1α, β and γ, also known as CBX5, CBX1 and CBX3, respectively). ASH1L facilitates the formation of open chromatin competent for CENP-A assembly on alphoid DNA. These results indicate that CENP-B is a nexus for histone modifiers that alternatively promote or suppress CENP-A assembly by mutually exclusive mechanisms. Besides the DNA-binding domain, the CENP-B acidic domain also facilitates CENP-A assembly de novo on transfected alphoid DNA. CENP-B therefore balances CENP-A assembly and heterochromatin formation on satellite DNA.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Otake K,Ohzeki JI,Shono N,Kugou K,Okazaki K,Nagase T,Yamakawa H,Kouprina N,Larionov V,Kimura H,Earnshaw WC,Masumoto H

doi

10.1242/jcs.243303

subject

Has Abstract

pub_date

2020-08-11 00:00:00

issue

15

eissn

0021-9533

issn

1477-9137

pii

jcs.243303

journal_volume

133

pub_type

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