Chromatin modification and higher-order chromosome structure play key roles in gene regulation, but their functional interplay in controlling gene expression is elusive. We have discovered the machinery and mechanism underlying the dynamic enrichment of histone modification H4K20me1 on hermaphrodite X chromosomes during C. elegans dosage compensation and demonstrated H4K20me1's pivotal role in regulating higher-order chromosome structure and X-chromosome-wide gene expression. The structure and the activity of the dosage compensation complex (DCC) subunit DPY-21 define a Jumonji demethylase subfamily that converts H4K20me2 to H4K20me1 in worms and mammals. Selective inactivation of demethylase activity eliminates H4K20me1 enrichment in somatic cells, elevates X-linked gene expression, reduces X chromosome compaction, and disrupts X chromosome conformation by diminishing the formation of topologically associating domains (TADs). Unexpectedly, DPY-21 also associates with autosomes of germ cells in a DCC-independent manner to enrich H4K20me1 and trigger chromosome compaction. Our findings demonstrate the direct link between chromatin modification and higher-order chromosome structure in long-range regulation of gene expression.

中文翻译：

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通过组蛋白H4K20脱甲基酶动态控制X染色体的构象和抑制。

染色质修饰和高阶染色体结构在基因调控中起着关键作用，但是它们在控制基因表达中的功能相互作用却难以捉摸。我们已经发现线虫剂量补偿期间在雌雄同体X染色体上组蛋白修饰H4K20me1动态富集的机制和机制，并证明了H4K20me1在调节高阶染色体结构和X染色体全基因表达中的关键作用。剂量补偿复合物（DCC）亚基DPY-21的结构和活性定义了Jumonji脱甲基酶亚家族，它将蠕虫和哺乳动物中的H4K20me2转换为H4K20me1。脱甲基酶活性的选择性失活消除了H4K20me1在体细胞中的富集，提高了X连锁基因的表达，减少了X染色体的紧缩，并通过减少拓扑关联域（TAD）的形成来破坏X染色体构象。出乎意料的是，DPY-21还以不依赖DCC的方式与生殖细胞常染色体相关联，以富集H4K20me1并触发染色体紧缩。我们的发现表明，在基因表达的长期调控中，染色质修饰与高级染色体结构之间存在直接联系。