CENP-H-containing Complex Facilitates Centromere Deposition of CENP-A in Cooperation with FACT and CHD1
CENP-H-containing Complex Facilitates Centromere Deposition of CENP-A in Cooperation with FACT and CHD1
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DOI：
10.1091/mbc.e09-01-0065
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发表时间：
2009-09-15
影响因子：
3.3
通讯作者：
Fukagawa, Tatsuo
中科院分区：
文献类型：
--
作者：
Okada, Masahiro;Okawa, Katsuya;Fukagawa, Tatsuo
着丝粒身份被认为是由表观遗传机制决定的。着丝粒特异性组蛋白H3变体CENP-A在指定构建着丝粒的位点中起核心作用。然而，CENP-A靶向着丝粒染色质的确切机制知之甚少。在这里，我们表明，促进染色质转录（FACT）定位于着丝粒在CENP-H-含有复杂的依赖性方式。在SSRP 1（FACT的一个亚基）的条件突变细胞系中，新合成的CENP-A的着丝粒靶向受到严重抑制。染色质重塑因子CHD 1在体内和体外均与SSRP 1结合，并与着丝粒结合。在SSRP 1缺失的细胞中，CHD 1的着丝粒定位丢失。CHD 1的RNA干扰敲低导致着丝粒定位的CENP-A的量减少。这些发现表明，CENP-H-含有复合物促进沉积新合成的CENP-A到着丝粒染色质与FACT和CHD 1合作。
Centromere identity is thought to be determined by epigenetic mechanisms. The centromere-specific histone H3 variant CENP-A plays a central role in specifying the locus where the centromere is constructed. However, the precise mechanisms that target CENP-A to centromeric chromatin are poorly understood. Here, we show that facilitates chromatin transcription (FACT) localizes to centromeres in a CENP-H-containing complex-dependent manner. In conditional mutant cell lines for SSRP1, a subunit of FACT, centromere targeting of newly synthesized CENP-A is severely inhibited. The chromatin remodeling factor CHD1 binds to SSRP1 both in vivo and in vitro and associates with centromeres. The centromeric localization of CHD1 is lost in SSRP1-depleted cells. RNA interference knockdown of CHD1 leads to a decrease in the amount of centromere localized CENP-A. These findings indicate that the CENP-H-containing complex facilitates deposition of newly synthesized CENP-A into centromeric chromatin in cooperation with FACT and CHD1.