Role of Swi6/HP1 Self-association-mediated Recruitment of Clr4/Suv39 in Establishment and Maintenance of Heterochromatin in Fission Yeast
Role of Swi6/HP1 Self-association-mediated Recruitment of Clr4/Suv39 in Establishment and Maintenance of Heterochromatin in Fission Yeast
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DOI：
10.1074/jbc.m110.143198
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发表时间：
2011-03-18
影响因子：
4.8
通讯作者：
Singh, Jagmohan
中科院分区：
文献类型：
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作者：
Haldar, Swati;Saini, Ashok;Singh, Jagmohan
Swi 6/HP 1是一个进化上保守的蛋白质，在裂殖酵母和高等真核生物中异染色质组装过程中起重要作用。在裂殖酵母中，通过组蛋白脱乙酰酶进行的组蛋白脱乙酰化被认为是随后通过组蛋白甲基转移酶Clr 4/Suv 39 H1进行的H3-Lys-9甲基化。H3-Lys-9-Me 2与Swi 6/HP 1的染色体结构域相互作用。Swi 6/HP 1被认为在Clr 4/Suv 39的下游起作用，并且Swi 6/HP 1的进一步自缔合被认为稳定异染色质结构。在这里，我们表明，自关联缺陷突变体Swi 6不与Clr 4相互作用。它不仅不能定位于异染色质基因座，而且还干扰H3-Lys-9-Me 2（从而Clr 4）和内源性Swi 6的异染色质定位在显性负性的方式。因此，Swi 6/HP 1的自缔合有助于与Clr 4结合和募集，从而通过协调而不是顺序机制建立和维持异染色质。
Swi6/HP1, an evolutionarily conserved protein, is critical for heterochromatin assembly in fission yeast and higher eukaryotes. In fission yeast, histone deacetylation by histone deacetylases is thought to be followed by H3-Lys-9 methylation by the histone methyltransferase Clr4/Suv39H1.H3-Lys-9-Me2 interacts with the chromodomain of Swi6/HP1. Swi6/HP1 is thought to act downstream of Clr4/Suv39, and further self-association of Swi6/HP1 is assumed to stabilize the heterochromatin structure. Here, we show that the self-association-defective mutant of Swi6 does not interact with Clr4. It not only fails to localize to heterochromatin loci but also interferes with heterochromatic localization of H3-Lys-9-Me2 (and thereby Clr4) and the endogenous Swi6 in a dominant negative manner. Thus, self-association of Swi6/HP1 helps in binding to and recruitment of Clr4 and thereby in establishment and maintenance of heterochromatin by a concerted rather than a sequential mechanism.