The 19S proteasome subunit Rpt3 regulates distribution of CENP-A by associating with centromeric chromatin
The 19S proteasome subunit Rpt3 regulates distribution of CENP-A by associating with centromeric chromatin
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DOI：
10.1038/ncomms4597
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发表时间：
2014-04-01
影响因子：
16.6
通讯作者：
Matsumoto, Tomohiro
中科院分区：
文献类型：
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作者：
Kitagawa, Teppei;Ishii, Kojiro;Matsumoto, Tomohiro
CENP-A是组蛋白H3的一种变体，被掺入到着丝粒染色质中，并在动粒建立过程中发挥作用。在裂殖酵母中，CENP-A的定位仅限于着丝粒核心结构域的10-20 kb区域。在这里，我们报告了一个突变体（rpt 3 -1），其中该区域扩展到40-70 kb。可能由于CENP-A的异常分布，该突变体表现出染色体不稳定性和增强的基因沉默。有趣的是，rpt 3（+）基因编码19 S蛋白酶体的一个亚基，该亚基定位于核膜。尽管Rpt 3与着丝粒染色质相关，但突变蛋白已经失去了这种定位。编码蛋白酶体与核膜的锚的cut 8（+）基因的缺失导致与在rpt 3 -1突变体中观察到的相似的表型。因此，我们建议蛋白酶体（或其亚复合物）与着丝粒染色质和调节CENP-A的分布。
CENP-A, a variant of histone H3, is incorporated into centromeric chromatin and plays a role during kinetochore establishment. In fission yeast, the localization of CENP-A is limited to a region spanning 10-20 kb of the core domain of the centromere. Here, we report a mutant (rpt3-1) in which this region is expanded to 40-70 kb. Likely due to abnormal distribution of CENP-A, this mutant exhibits chromosome instability and enhanced gene silencing. Interestingly, the rpt3(+) gene encodes a subunit of the 19S proteasome, which localizes to the nuclear membrane. Although Rpt3 associates with centromeric chromatin, the mutant protein has lost this localization. A loss of the cut8(+) gene encoding an anchor of the proteasome to the nuclear membrane causes similar phenotypes as observed in the rpt3-1 mutant. Thus, we propose that the proteasome (or its subcomplex) associates with centromeric chromatin and regulates distribution of CENP-A.