Induction of H3K9me3 and DNA methylation by tethered heterochromatin factors in Neurospora crassa
Induction of H3K9me3 and DNA methylation by tethered heterochromatin factors in Neurospora crassa
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DOI：
10.1073/pnas.1715049114
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发表时间：
2017-11-07
影响因子：
11.1
通讯作者：
Selker, Eric U.
中科院分区：
文献类型：
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作者：
Gessaman, Jordan D.;Selker, Eric U.
功能不同的染色质结构域显示不同的化学标记。组成型异染色质通常与组蛋白H3上赖氨酸9的三甲基化（H3K9me3）、低乙酰化组蛋白和DNA甲基化相关，但这些特征的贡献和相互作用尚未完全了解。为了剖析异染色质的建立，我们研究了这些功能之间的关系，使用在粗糙脉孢菌体内拴系系统。H3K9甲基转移酶DIM-5（甲基化-5缺陷）的人工募集在正常活性的常染色质基因座处诱导H3K9me3和DNA甲基化，但没有绕过先前涉及DIM-5定位的DIM-7的要求，表明额外的DIM-7功能。系留异染色质蛋白1（HP1）诱导H3K9me3，DNA甲基化和基因沉默。诱导的异染色质需要组蛋白脱乙酰基酶1（HDA-1），与一个完整的催化结构域，但HDA-1是不必要的从头异染色质形成在天然异染色质区域。沉默不需要H3K9me3或DNA甲基化。然而，DNA甲基化有助于由系留的HP 1诱导的H3K9me3的建立。我们的分析还揭示了依赖于HDA-1和DIM-5的调节机制的证据，以控制DNA甲基转移酶DIM-2的定位和催化活性。我们的研究阐明了异染色质的典型方面之间的相互关系，并支持HDA-1介导的组蛋白去乙酰化在异染色质扩散和基因沉默中的核心作用。
Functionally different chromatin domains display distinct chemical marks. Constitutive heterochromatin is commonly associated with trimethylation of lysine 9 on histone H3 (H3K9me3), hypoacetylated histones, and DNA methylation, but the contributions of and interplay among these features are not fully understood. To dissect the establishment of heterochromatin, we investigated the relationships among these features using an in vivo tethering system in Neurospora crassa. Artificial recruitment of the H3K9 methyltransferase DIM-5 (defective in methylation-5) induced H3K9me3 and DNA methylation at a normally active, euchromatic locus but did not bypass the requirement of DIM-7, previously implicated in the localization of DIM-5, indicating additional DIM-7 functionality. Tethered heterochromatin protein 1 (HP1) induced H3K9me3, DNA methylation, and gene silencing. The induced heterochromatin required histone deacetylase 1 (HDA-1), with an intact catalytic domain, but HDA-1 was not essential for de novo heterochromatin formation at native heterochromatic regions. Silencing did not require H3K9me3 or DNA methylation. However, DNA methylation contributed to establishment of H3K9me3 induced by tethered HP1. Our analyses also revealed evidence of regulatory mechanisms, dependent on HDA-1 and DIM-5, to control the localization and catalytic activity of the DNA methyltransferase DIM-2. Our study clarifies the interrelationships among canonical aspects of heterochromatin and supports a central role of HDA-1-mediated histone deacetylation in heterochromatin spreading and gene silencing.