Uncoupling the distinct functions of HP1 proteins during heterochromatin establishment and maintenance.
Uncoupling the distinct functions of HP1 proteins during heterochromatin establishment and maintenance.
复制标题
在异染色质建立和维持过程中解偶联 HP1 蛋白的独特功能。
DOI：
10.1101/2023.04.30.538869
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Ragunathan,Kaushik
中科院分区：
文献类型：
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作者：
Seman,Melissa;Levashkevich,Alexander;Larkin,Ajay;Huang,Fengting;Ragunathan,Kaushik
H3K9甲基化（H3K9me）标记称为异染色质的转录沉默基因组区域。一类保守的HP1蛋白是建立和维持异染色质所必需的。HP1蛋白结合H3K9me，募集促进异染色质形成的因子，并寡聚化形成相分离的缩合物。我们不知道HP1蛋白如何结合异染色质建立和维持转录沉默。在这里，我们证明了S。当H3K4甲基转移酶Set1和H3K14乙酰转移酶Mst2缺失时，粟酒裂殖酵母HP1同源物Swi6可以被完全绕过以在异位和内源基因座处建立沉默。删除Set1和Mst2增强Clr4酶活性，导致更高的H3K9me水平和增加的扩散。相反，Swi6和它的能力寡聚化是不可或缺的表观遗传维持。我们的研究结果表明，HP1蛋白在调节组蛋白修饰串扰建立过程中的作用，并确定了一个遗传分离的功能，在维持表观遗传记忆。
H3K9 methylation (H3K9me) marks transcriptionally silent genomic regions called heterochromatin. A conserved class of HP1 proteins are critically required to establish and maintain heterochromatin. HP1 proteins bind to H3K9me, recruit factors that promote heterochromatin formation, and oligomerize to form phase-separated condensates. We do not understand how HP1 protein binding to heterochromatin establishes and maintains transcriptional silencing. Here, we demonstrate that the S. pombe HP1 homolog, Swi6, can be completely bypassed to establish silencing at ectopic and endogenous loci when an H3K4 methyltransferase, Set1 and an H3K14 acetyltransferase, Mst2 are deleted. Deleting Set1 and Mst2 enhances Clr4 enzymatic activity, leading to higher H3K9me levels and increased spreading. In contrast, Swi6 and its capacity to oligomerize were indispensable during epigenetic maintenance. Our results demonstrate the role of HP1 proteins in regulating histone modification crosstalk during establishment and identifies a genetically separable function in maintaining epigenetic memory.