CENP-B creates alternative epigenetic chromatin states permissive for CENP-A or heterochromatin assembly
CENP-B creates alternative epigenetic chromatin states permissive for CENP-A or heterochromatin assembly
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DOI：
10.1242/jcs.243303
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发表时间：
2020-01
影响因子：
4
通讯作者：
Koichiro Otake;Jun-ichirou Ohzeki;Nobuaki Shono;Kazuto Kugou;K. Okazaki;T. Nagase;H. Yamakawa;N. Kouprin
中科院分区：
文献类型：
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作者：
Koichiro Otake;Jun-ichirou Ohzeki;Nobuaki Shono;Kazuto Kugou;K. Okazaki;T. Nagase;H. Yamakawa;N. Kouprin
摘要CENP-B与着丝粒卫星DNA上的CENP-B盒结合。CENP-B通过与CENP-A核小体和CENP-C相互作用维持着动粒功能。CENP-B与转染体DNA结合可诱导CENP-A从头组装、功能着丝粒和着丝粒形成，以及随后的人类人工染色体(HAC)的形成。此外，CENP-B还促进了组蛋白H3K9(组蛋白H3赖氨酸9)在异位Alphid DNA整合位点上由SUV39H1介导的三甲基化。过多的异染色质侵入着丝粒染色质抑制CENP-A组装。目前尚不清楚CENP-B是如何控制这种不同的染色质状态的。在这里，我们发现CENP-B酸性结构域招募了组蛋白伴侣蛋白和许多染色质修饰物，包括H3K36甲基酶Ash11，以及异染色质成分SUV39H1和HP1(HP1α，β和γ，分别称为CBX5、CBX1和CBX3)。Ash1促进开放染色质的形成，使其能够在Alphid DNA上组装CENP-A。这些结果表明，CENP-B是组蛋白修饰剂的纽带，组蛋白修饰剂通过相互排斥的机制促进或抑制CENP-A的组装。除DNA结合区外，CENP-B酸性结构域还促进CENP-A在转染体DNA上的从头组装。因此，CENP-B平衡了CENP-A组装和卫星DNA上异染色质的形成。摘要：CENP-B的酸性结构域促进了各种蛋白质在着丝粒卫星DNA上的组装，包括HP1和Ash11。CENP-B控制着丝粒表观遗传状态。
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. Summary: The acidic domain of CENP-B facilitates assembly of various proteins at centromeric satellite DNA, including HP1 and ASH1L. CENP-B controls centromere epigenetic status.