Elaboration, Diversification and Regulation of the Sir1 Family of Silencing Proteins in Saccharomyces
Elaboration, Diversification and Regulation of the Sir1 Family of Silencing Proteins in Saccharomyces
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DOI：
10.1534/genetics.108.099663
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发表时间：
2009-04-01
期刊：
影响因子：
3.3
通讯作者：
Rine, Jasper
中科院分区：
文献类型：
--
作者：
Gallagher, Jennifer E. G.;Babiarz, Joshua E.;Rine, Jasper
异染色质使染色体的结构域在转录上沉默，并且由于其形成中的克隆变异，可以产生遗传上不同的遗传相同细胞群体。酿酒酵母的Sir 1主要在HMR和HML基因座异染色质沉默的建立中起作用，但不是维持。在几个酵母属物种中，我们发现了Sir 1的多个旁系同源物，称为Kos 1-Kos 4（Sir 1的Kin）。科斯和Sir 1蛋白在沉默S. bayanus这些旁系同源物的突变体减少沉默在HML比在HAM。SIR 1家族的大多数基因位于端粒附近，并且至少有一个基因受端粒位置效应调节。In S.在酿酒酵母中，Sir 1通过其ORC相互作用区（OIR）被募集到HML和HMR的沉默子中，OIR结合Orc 1的溴邻近同源（BAH）结构域。鲁氏接合酵母在沉默交配盒出现后，但在全基因组复制之前，从酵母中分化出来，含有Kos 3的直系同源物，显然是家族的原型成员，只有一个OIR。相反，Sir 1，Kos 1，Kos 2和Kos 4的所有直系同源物中都存在这个结构域的复制。我们建议，Sir 3的功能专业化，本身是一个paradox的Orc 1，作为一个沉默蛋白是由Sir 1家族中的OIR结构域的串联重复，允许不同的Sir 1-Sir 3和Sir 1-Orc 1的相互作用，通过OIR-BAH结构域的相互作用促进。
Heterochromatin renders domains of chromosomes transcriptionally silent and, due to clonal variation in its formation, can generate heritably distinct populations of genetically identical cells. Saccharomyces cerevisiae's Sir1 functions primarily in the establishment, but not the maintenance, of heterochromatic silencing at the HMR and HML loci. In several Saccharomyces species, we discovered multiple paralogs of Sir1, called Kos1-Kos4 (Kin of Sir1). The Kos and Sir1 proteins contributed partially overlapping functions to silencing of both cryptic mating loci in S. bayanus. Mutants of these paralogs reduced silencing at HML more than at HAM Most genes of the SIR1 family were located near telomeres, and at least one paralog was regulated by telomere position effect. In S. cerevisiae, Sir1 is recruited to the silencers at HML and HMR via its ORC interacting region (OIR), which binds the bromo adjacent homology (BAH) domain of Orc1. Zygosaccharomyces rouxii, which diverged from Saccharomyces after the appearance of the silent mating cassettes, but before the whole-genome duplication, contained an ortholog of Kos3 that was apparently the archetypal member of the family, with only one OIR. In contrast, a duplication of this domain was present in all orthologs of Sir1, Kos1, Kos2, and Kos4. We propose that the functional specialization of Sir3, itself a paralog of Orc1, as a silencing protein was facilitated by the tandem duplication of the OIR domain in the Sir1 family, allowing distinct Sir1-Sir3 and Sir1-Orc1 interactions through OIR-BAH domain interactions.