RbAp46/48LIN-53 Is Required for Holocentromere Assembly in Caenorhabditis elegans
RbAp46/48LIN-53 Is Required for Holocentromere Assembly in Caenorhabditis elegans
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DOI：
10.1016/j.celrep.2016.01.065
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发表时间：
2016-03-01
期刊：
影响因子：
8.8
通讯作者：
Yuen, Karen Wing Yee
中科院分区：
文献类型：
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作者：
Lee, Bernard Chi Hang;Lin, Zhongyang;Yuen, Karen Wing Yee
着丝粒是用于募集动粒和指导染色体分离的专门染色体区域，其表观遗传学标记为着丝粒组蛋白H3变体CENP-A。为了在整个细胞周期中保持着丝粒的同一性，在DNA复制期间稀释的CENP-A被补充。已知许可因子M18 BP 1（KNL-2）将CENP-A招募到全着丝粒。在这里，我们表明，RbAp 46/48（LIN-53），一个保守的组蛋白伴侣，是必需的CENP-A（HCP-3）在全着丝粒秀丽隐杆线虫本地化。事实上，RbAp 46/48（LIN-53）和CENP-A（HCP-3）定位是相互依赖的。RbAp 46/48（LIN-53）在中期以CENP-A（HCP-3）和M18 BP 1（KNL-2）依赖性方式定位于着丝粒，表明CENP-A（HCP-3）加载可能发生在后期之前。RbAp 46/48（LIN-53）不通过组蛋白乙酰化、H3 K27三甲基化或其已知的染色质修饰复合物在着丝粒处起作用。RbAp 46/48（LIN-53）可能独立地起护送CENP-A（HCP-3）进行全着丝粒组装的作用，但对于其他动粒蛋白的募集是不稳定的。然而，RbAp 46/48（LIN-53）的缺失导致后期桥和染色体错误分离。这项研究揭示了holocentromere装配层次和它的保护与monocentromeres。
Centromeres, the specialized chromosomal regions for recruiting kinetochores and directing chromosome segregation, are epigenetically marked by a centromeric histoneH3 variant, CENP-A. Tomaintain centromere identity through cell cycles, CENP-A diluted during DNA replication is replenished. The licensing factor M18BP1(KNL-2) is known to recruit CENP-A to holocentromeres. Here, we show that RbAp46/48(LIN-53), a conserved histone chaperone, is required for CENP-A(HCP-3) localization in holocentric Caenorhabditis elegans. Indeed, RbAp46/48(LIN-53) and CENP-A(HCP-3) localizations are interdependent. RbAp46/48(LIN-53) localizes to the centromere during metaphase in a CENP-A(HCP-3) -and M18BP1(KNL-2) dependent manner, suggesting CENP-A(HCP-3) loading may occur before anaphase. RbAp46/48(LIN-53) does not function at the centromere through histone acetylation, H3K27 trimethylation, or its known chromatin-modifying complexes. RbAp46/48(LIN-53) may function independently to escort CENP-A(HCP-3) for holocentromere assembly but is dispensable for other kinetochore protein recruitment. Nonetheless, depletion of RbAp46/48(LIN-53) leads to anaphase bridges and chromosome missegregation. This study unravels the holocentromere assembly hierarchy and its conservation with monocentromeres.