LSD1 prevents aberrant heterochromatin formation in Neurospora crassa.
LSD1 prevents aberrant heterochromatin formation in Neurospora crassa.
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DOI：
10.1093/nar/gkaa724
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发表时间：
2020-10-09
影响因子：
14.9
通讯作者：
Selker EU
中科院分区：
文献类型：
--
作者：
Storck WK;Bicocca VT;Rountree MR;Honda S;Ormsby T;Selker EU
异染色质是一种特殊形式的染色质，它限制了DNA的接触，抑制了包括转录和重组在内的遗传过程。在粗神经孢子虫中，组成型异染色质的特征是组蛋白H3上赖氨酸9的三甲基化、组蛋白的低乙酰化和DNA甲基化。我们探讨了保守的组蛋白去甲基化酶，赖氨酸特异性去甲基化酶1 （LSD1）是否调节神经孢子虫的异染色质，如果是，如何调节。虽然LSD1参与异染色质调节，但其功能在不同的系统中是不一致的；LSD1的同源物已被证明分别通过去除H3K4me或H3K9me来促进或拮抗异染色质扩张。我们确定了神经孢子虫LSD复合体（LSDC）的三个成员：LSD1， PHF1和BDP-1。缺乏这些蛋白质的菌株表现出异染色质的可变扩散和在整个基因组中建立新的异染色质结构域。虽然在神经孢子虫中，H3K9me3的建立通常独立于DNA甲基化，但在典型异染色质区域之外发现了DNA甲基化依赖性H3K9me3的实例。与此一致的是，Δlsd1菌株的hyper-H3K9me3表型依赖于DNA甲基化的存在，以及hchc介导的组蛋白去乙酰化，这表明传播依赖于某种反馈机制。总之，我们的结果表明LSD1与HCHC相反，以维持适当的异染色质边界。
Heterochromatin is a specialized form of chromatin that restricts access to DNA and inhibits genetic processes, including transcription and recombination. In Neurospora crassa, constitutive heterochromatin is characterized by trimethylation of lysine 9 on histone H3, hypoacetylation of histones, and DNA methylation. We explored whether the conserved histone demethylase, lysine-specific demethylase 1 (LSD1), regulates heterochromatin in Neurospora, and if so, how. Though LSD1 is implicated in heterochromatin regulation, its function is inconsistent across different systems; orthologs of LSD1 have been shown to either promote or antagonize heterochromatin expansion by removing H3K4me or H3K9me respectively. We identify three members of the Neurospora LSD complex (LSDC): LSD1, PHF1, and BDP-1. Strains deficient for any of these proteins exhibit variable spreading of heterochromatin and establishment of new heterochromatin domains throughout the genome. Although establishment of H3K9me3 is typically independent of DNA methylation in Neurospora, instances of DNA methylation-dependent H3K9me3 have been found outside regions of canonical heterochromatin. Consistent with this, the hyper-H3K9me3 phenotype of Δlsd1 strains is dependent on the presence of DNA methylation, as well as HCHC-mediated histone deacetylation, suggesting that spreading is dependent on some feedback mechanism. Altogether, our results suggest LSD1 works in opposition to HCHC to maintain proper heterochromatin boundaries.
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DOI：
10.1073/pnas.1715049114
发表时间：
2017-11-07
影响因子：
11.1
作者：
Gessaman, Jordan D.;Selker, Eric U.
通讯作者：
Selker, Eric U.
影响因子：
64.8
作者：
COVENEY, J;WOODLAND, HR
通讯作者：
WOODLAND, HR
影响因子：
7
作者：
Jamieson K;Wiles ET;McNaught KJ;Sidoli S;Leggett N;Shao Y;Garcia BA;Selker EU
通讯作者：
Selker EU
DOI：
10.1073/pnas.0813063106
发表时间：
2009-06-02
影响因子：
11.1
作者：
Fischer, Tamas;Cui, Bowen;Grewal, Shiv I. S.
通讯作者：
Grewal, Shiv I. S.
组蛋白H3K9ME国家在RNAi中的独特作用和可遗传的转录沉默。
影响因子：
64.8
作者：
Jih G;Iglesias N;Currie MA;Bhanu NV;Paulo JA;Gygi SP;Garcia BA;Moazed D
通讯作者：
Moazed D