Xenopus laevis M18BP1 Directly Binds Existing CENP-A Nucleosomes to Promote Centromeric Chromatin Assembly.

Xenopus laevis M18BP1 Directly Binds Existing CENP-A Nucleosomes to Promote Centromeric Chromatin Assembly.
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DOI:
10.1016/j.devcel.2017.06.021
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发表时间:
2017-07-24
期刊:
影响因子:
11.8
通讯作者:
Straight AF
Straight AF
中科院分区:
生物学1区
文献类型:
--
作者:
French BT;Westhorpe FG;Limouse C;Straight AF

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脊椎动物的着丝粒由含有组蛋白H3变体CENP-A的核小体表观遗传学定义。CENP-A核小体组装需要三蛋白Mis18复合物(Mis18 α,Mis18 β和M18BP1),该复合物将CENP-A伴侣HJURP募集到着丝粒,但Mis18复合物如何识别着丝粒染色质尚不清楚。使用非洲爪蟾卵提取物,我们表明,直接的,细胞周期调节的结合M18BP1 CENP-A核小体招募Mis18复杂的间期着丝粒,以促进新的CENP-A核小体组装。我们证明,非洲爪蟾M18BP1结合CENP-A核小体使用的基序,是广泛保守的,除了在哺乳动物。M18 BP 1基序类似于CENP-C中的CENP-A核小体结合基序,并且我们表明CENP-C与M18 BP 1竞争CENP-A核小体在着丝粒处的结合。我们发现CENP-C和M18BP1都将HJURP招募到着丝粒中进行新的CENP-A组装。这项研究定义了招募CENP-A组装因子到现有CENP-A核小体中用于着丝粒表观遗传的细胞机制。
Vertebrate centromeres are epigenetically defined by nucleosomes containing the histone H3 variant, CENP-A. CENP-A nucleosome assembly requires the three-protein Mis18 complex (Mis18α, Mis18β, and M18BP1) that recruits the CENP-A chaperone HJURP to centromeres, but how the Mis18 complex recognizes centromeric chromatin is unknown. Using Xenopus egg extract, we show that direct, cell cycle-regulated binding of M18BP1 to CENP-A nucleosomes recruits the Mis18 complex to interphase centromeres to promote new CENP-A nucleosome assembly. We demonstrate that Xenopus M18BP1 binds CENP-A nucleosomes using a motif that is widely conserved except in mammals. The M18BP1 motif resembles a CENP-A nucleosome binding motif in CENP-C, and we show that CENP-C competes with M18BP1 for CENP-A nucleosome binding at centromeres. We show that both CENP-C and M18BP1 recruit HJURP to centromeres for new CENP-A assembly. This study defines cellular mechanisms for recruiting CENP-A assembly factors to existing CENP-A nucleosomes for the epigenetic inheritance of centromeres.
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