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CENP-B creates alternative epigenetic chromatin states permissive for CENP-A or heterochromatin assembly.
Journal of Cell Science ( IF 4 ) Pub Date : 2020-08-11 , DOI: 10.1242/jcs.243303
Koichiro Otake 1 , Jun-Ichirou Ohzeki 1 , Nobuaki Shono 1 , Kazuto Kugou 1 , Koei Okazaki 1 , Takahiro Nagase 2 , Hisashi Yamakawa 3 , Natalay Kouprina 4 , Vladimir Larionov 4 , Hiroshi Kimura 5 , William C Earnshaw 6 , Hiroshi Masumoto 7
Affiliation  

Koichiro Otake, Jun-ichirou Ohzeki, Nobuaki Shono, Kazuto Kugou, Koei Okazaki, Takahiro Nagase, Hisashi Yamakawa, Natalay Kouprina, Vladimir Larionov, Hiroshi Kimura, William C. Earnshaw, and Hiroshi Masumoto

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 , 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.



中文翻译:

CENP-B 创建允许 CENP-A 或异染色质组装的替代表观遗传染色质状态。

Koichiro Otake、Jun-ichirou Ohzeki、Nobuaki Shono、Kazuto Kugou、Koei Okazaki、Takahiro Nagase、Hisashi Yamakawa、Natalay Kouprina、Vladimir Larionov、Hiroshi Kimura、William C. Earnshaw 和 Hiroshi Masumoto

CENP-B 与着丝粒卫星 DNA(在人类中称为 alphoid DNA)上的 CENP-B 盒结合。CENP-B 通过与 CENP-A 核小体和 CENP-C 相互作用来维持动粒功能。CENP-B 与转染的 alphoid DNA 结合可以诱导CENP-A 从头组装、功能性着丝粒和动粒形成,以及随后的人类人工染色体 (HAC) 形成此外,CENP-B 还可以在 Suv39h1 的介导下,在异位 alphoid DNA 整合位点促进 alphoid DNA 上的 H3K9(组蛋白 H3 赖氨酸 9)三甲基化。过多的异染色质侵入着丝粒染色质会抑制 CENP-A 组装。目前尚不清楚 CENP-B 如何控制如此不同的染色质状态。在这里,我们表明 CENP-B 酸性结构域招募组蛋白伴侣和许多染色质修饰剂,包括 H3K36 甲基化酶 ASH1L,以及异染色质成分 Suv39h1 和 HP1(HP1α、β 和 ,也分别称为 CBX5、CBX1 和 CBX3) )。ASH1L 促进开放染色质的形成,该染色质能够在 alphoid DNA 上组装 CENP-A。这些结果表明 CENP-B 是组蛋白修饰剂的一个纽带,组蛋白修饰剂通过相互排斥的机制交替促进或抑制 CENP-A 组装。除了 DNA 结合结构域外,CENP-B 酸性结构域还促进 CENP-A在转染的 alpoid DNA 上从头组装。因此,CENP-B 平衡卫星 DNA 上的 CENP-A 组装和异染色质形成。

更新日期:2020-08-17
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