Open AccessCENP-B creates alternative epigenetic chromatin states permissive for CENP-A or heterochromatin assembly
Author(s) -
Kazuo Otake,
Jun-ichirou Ohzeki,
Nobuaki Shono,
Kazuto Kugou,
Keishi Okazaki,
Takahiro Nagase,
Hisashi Yamakawa,
Natalay Kouprina,
Vladimir Larionov,
Hiroshi Kimurâ,
William C. Earnshaw,
Hiroshi Masumoto
Publication year - 2020
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.243303
Subject(s) - biology , chromatin , heterochromatin , centromere , heterochromatin protein 1 , histone h3 , nucleosome , microbiology and biotechnology , histone , genetics , kinetochore , chromodomain , dna , chromosome , gene , helicase , rna
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.