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.

中文翻译：

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LSD1防止在神经孢霉中异常异染色质形成。

异染色质是染色质的一种特殊形式，它限制了DNA的访问并抑制了遗传过程，包括转录和重组。在神经孢霉中组成型异染色质的特征在于组蛋白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脱甲基酶，赖氨酸特异性脱甲基酶1（LSD1）是否调节Neurospora中的异染色质，如果是，如何进行。尽管LSD1涉及异染色质调节，但其功能在不同系统中不一致。LSD1的直系同源物已显示出通过分别去除H3K4me或H3K9me来促进或拮抗异染色质的扩增。我们确定了Neurospora LSD复合体（LSDC）的三个成员：LSD1，PHF1和BDP-1。缺乏这些蛋白的菌株在整个基因组中表现出异染色质的可变扩散和新异染色质结构域的建立。尽管H3K9me3的建立通常独立于Neurospora中的DNA甲基化，但已发现在规范异染色质区域之外存在DNA甲基化依赖性H3K9me3。与此相符的是Δ的超H3K9me3表型lsd1菌株取决于DNA甲基化的存在以及HCHC介导的组蛋白去乙酰化，这表明传播取决于某些反馈机制。总而言之，我们的结果表明LSD1与HCHC相反，以维持适当的异染色质边界。