Nap1 regulates proper CENP-B binding to nucleosomes.
Nap1 regulates proper CENP-B binding to nucleosomes.
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DOI：
10.1093/nar/gks1464
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发表时间：
2013-03-01
影响因子：
14.9
通讯作者：
Kurumizaka H
中科院分区：
文献类型：
--
作者：
Tachiwana H;Miya Y;Shono N;Ohzeki J;Osakabe A;Otake K;Larionov V;Earnshaw WC;Kimura H;Masumoto H;Kurumizaka H
CENP-B是一种广泛保守的着丝粒卫星DNA结合蛋白，它特异性地结合一个17 bp的DNA序列，称为CENP-B盒。CENP-B在着丝粒核小体的从头组装中发挥积极作用，其中包含着丝粒特异性组蛋白H3变体CENP-A。同时，CENP-B还通过整合到异位位点的卫星DNA上的异染色质形成阻止了CENP-A核小体的非期望组装。因此，不适当的与染色体结合可能是有害的。然而，目前还没有关于CENP-B驱逐机制的报道。在本研究中，我们发现人类酸性组蛋白伴侣蛋白Nap1抑制了CENP-B与核小体的非特异性结合，并明显刺激了CENP-B与核小体中同源的CENP-B盒DNA的结合。在人类细胞中，模型实验证实了Nap1对CENP-B的清除活性，当Nap1拴在人类人工染色体或携带CENP-B盒子的异位染色体位点附近时，与CENP-B结合的能力显著降低。相比之下，另一种酸性组蛋白伴侣sNASP在体外和体内都没有促进CENP-B的排出，也没有刺激特异性的CENP-B与CENP-A核小体的结合。因此，我们提出了一种由Nap1调控CENP-B的新机制。
CENP-B is a widely conserved centromeric satellite DNA-binding protein, which specifically binds to a 17-bp DNA sequence known as the CENP-B box. CENP-B functions positively in the de novo assembly of centromeric nucleosomes, containing the centromere-specific histone H3 variant, CENP-A. At the same time, CENP-B also prevents undesired assembly of the CENP-A nucleosome through heterochromatin formation on satellite DNA integrated into ectopic sites. Therefore, improper CENP-B binding to chromosomes could be harmful. However, no CENP-B eviction mechanism has yet been reported. In the present study, we found that human Nap1, an acidic histone chaperone, inhibited the non-specific binding of CENP-B to nucleosomes and apparently stimulated CENP-B binding to its cognate CENP-B box DNA in nucleosomes. In human cells, the CENP-B eviction activity of Nap1 was confirmed in model experiments, in which the CENP-B binding to a human artificial chromosome or an ectopic chromosome locus bearing CENP-B boxes was significantly decreased when Nap1 was tethered near the CENP-B box sequence. In contrast, another acidic histone chaperone, sNASP, did not promote CENP-B eviction in vitro and in vivo and did not stimulate specific CENP-B binding to CENP-A nucleosomes in vitro. We therefore propose a novel mechanism of CENP-B regulation by Nap1.
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影响因子：
16
作者：
Camahort, Raymond;Shivaraju, Manjunatha;Mattingly, Mark;Li, Bing;Nakanishi, Shima;Zhu, Dongxiao;Shilatifard, Ali;Workman, Jerry L.;Gerton, Jennifer L.
通讯作者：
Gerton, Jennifer L.
影响因子：
9.8
作者：
Dalal Y;Wang H;Lindsay S;Henikoff S
通讯作者：
Henikoff S
影响因子：
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作者：
Dorn, Jonas F.;Maddox, Paul S.
通讯作者：
Maddox, Paul S.
影响因子：
64.5
作者：
Hori, Tetsuya;Amano, Miho;Fukagawa, Tatsuo
通讯作者：
Fukagawa, Tatsuo
影响因子：
64.5
作者：
Black BE;Cleveland DW
通讯作者：
Cleveland DW