Direct interrogation of the role of H3K9 in metazoan heterochromatin function.
Direct interrogation of the role of H3K9 in metazoan heterochromatin function.
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DOI：
10.1101/gad.286278.116
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发表时间：
2016-08-15
影响因子：
10.5
通讯作者：
Duronio RJ
中科院分区：
文献类型：
--
作者：
Penke TJ;McKay DJ;Strahl BD;Matera AG;Duronio RJ
异染色质的一个定义特征是组蛋白H3（H3K9me）的Lys9的甲基化，H3K9me是异染色质蛋白1（HP 1）的结合位点。Penke等人产生并分析了H3K9R突变果蝇，分离了H3K9甲基转移酶的H3K9和非组蛋白底物的功能。异染色质的一个定义特征是组蛋白H3（H3K9me）的Lys9的甲基化，H3K9me是异染色质蛋白1（HP 1）的结合位点。虽然H3K9甲基转移酶和HP1是异染色质结构所必需的，但H3K9对异染色质功能和动物发育的具体贡献尚不清楚。使用我们最近开发的平台在果蝇中设计组蛋白基因，我们产生了H3K9R突变果蝇，分离了H3K9甲基转移酶的H3K9和非组蛋白底物的功能。核小体占有率和HP1a在近着丝粒异染色质的结合显着减少H3K9R突变体。尽管染色体结构发生了这些变化，但仍有一小部分H3K9R突变体完成了发育。与此结果一致，大多数蛋白质编码基因的表达，包括异染色质内的那些，在H3K9R和对照之间是相似的。相反，H3K9R突变体表现出增加的开放染色质和来自皮尔纳簇和转座子的转录，导致转座子动员。因此，转座子沉默是H3K9的主要发育功能。
A defining feature of heterochromatin is methylation of Lys9 of histone H3 (H3K9me), a binding site for heterochromatin protein 1 (HP1). Penke et al. generated and analyzed H3K9R mutant flies, separating the functions of H3K9 and nonhistone substrates of H3K9 methyltransferases. A defining feature of heterochromatin is methylation of Lys9 of histone H3 (H3K9me), a binding site for heterochromatin protein 1 (HP1). Although H3K9 methyltransferases and HP1 are necessary for proper heterochromatin structure, the specific contribution of H3K9 to heterochromatin function and animal development is unknown. Using our recently developed platform to engineer histone genes in Drosophila, we generated H3K9R mutant flies, separating the functions of H3K9 and nonhistone substrates of H3K9 methyltransferases. Nucleosome occupancy and HP1a binding at pericentromeric heterochromatin are markedly decreased in H3K9R mutants. Despite these changes in chromosome architecture, a small percentage of H3K9R mutants complete development. Consistent with this result, expression of most protein-coding genes, including those within heterochromatin, is similar between H3K9R and controls. In contrast, H3K9R mutants exhibit increased open chromatin and transcription from piRNA clusters and transposons, resulting in transposon mobilization. Hence, transposon silencing is a major developmental function of H3K9.