Loss of HP1 causes depletion of H3K27me3 from facultative heterochromatin and gain of H3K27me2 at constitutive heterochromatin.
Loss of HP1 causes depletion of H3K27me3 from facultative heterochromatin and gain of H3K27me2 at constitutive heterochromatin.
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DOI：
10.1101/gr.194555.115
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发表时间：
2016-01
期刊：
影响因子：
7
通讯作者：
Selker EU
中科院分区：
文献类型：
--
作者：
Jamieson K;Wiles ET;McNaught KJ;Sidoli S;Leggett N;Shao Y;Garcia BA;Selker EU
组蛋白H3上的甲基化赖氨酸27(H3K27me)标志着抑制的“兼性异染色质”，包括植物和动物中发育调节的基因。H3K27me定位的机制在很大程度上是未知的，部分原因可能是表观遗传调控网络的复杂性。我们使用了一种相对简单的模式生物，同时具有兼性和结构性异染色质，粗毛脉孢菌，以探索异染色质元素之间可能的相互作用。在高等真核生物中，H3K9me3的减少和构成异染色质的DNA甲基化导致H3K27me3的重新分布的报道不一。在脉孢菌中，我们发现DCDC H3K9甲基化复合体的任何成员的消除导致H3K27me的分布发生了巨大的变化；兼性异染色质的区域丢失了H3K27me3，而通常由H3K9me3标记的区域在H3K27处发生了甲基化。DNA甲基化的消除对H3K27me的分布没有明显影响。HP1的消除也导致了H3K27me的分布发生了重大变化，表明HP1对于兼性异染色质的正常定位是重要的。由于HP1的缺失导致了H3K27me2/3的重新分布，而不是H3K9me3，这些通常不重叠的标记成为重叠的。事实上，质谱仪显示H3K9me3和H3K27me2在HPO菌株的H3分子上有很大程度的共生。失去H3K27me机制(例如，甲基转移酶SET-7)并没有影响构成异染色质，但部分挽救了DCDC突变体的缓慢生长，表明这些突变体的生长不良部分归因于异位H3K27me。总之，我们对脉孢子虫的发现阐明了真核生物中兼性异染色质和结构性异染色质的相互作用。
Methylated lysine 27 on histone H3 (H3K27me) marks repressed “facultative heterochromatin,” including developmentally regulated genes in plants and animals. The mechanisms responsible for localization of H3K27me are largely unknown, perhaps in part because of the complexity of epigenetic regulatory networks. We used a relatively simple model organism bearing both facultative and constitutive heterochromatin, Neurospora crassa, to explore possible interactions between elements of heterochromatin. In higher eukaryotes, reductions of H3K9me3 and DNA methylation in constitutive heterochromatin have been variously reported to cause redistribution of H3K27me3. In Neurospora, we found that elimination of any member of the DCDC H3K9 methylation complex caused massive changes in the distribution of H3K27me; regions of facultative heterochromatin lost H3K27me3, while regions that are normally marked by H3K9me3 became methylated at H3K27. Elimination of DNA methylation had no obvious effect on the distribution of H3K27me. Elimination of HP1, which “reads” H3K9me3, also caused major changes in the distribution of H3K27me, indicating that HP1 is important for normal localization of facultative heterochromatin. Because loss of HP1 caused redistribution of H3K27me2/3, but not H3K9me3, these normally nonoverlapping marks became superimposed. Indeed, mass spectrometry revealed substantial cohabitation of H3K9me3 and H3K27me2 on H3 molecules from an hpo strain. Loss of H3K27me machinery (e.g., the methyltransferase SET-7) did not impact constitutive heterochromatin but partially rescued the slow growth of the DCDC mutants, suggesting that the poor growth of these mutants is partly attributable to ectopic H3K27me. Altogether, our findings with Neurospora clarify interactions of facultative and constitutive heterochromatin in eukaryotes.