H4K20me3 is important for Ash1-mediated H3K36me3 and transcriptional silencing in facultative heterochromatin in a fungal pathogen.
H4K20me3 is important for Ash1-mediated H3K36me3 and transcriptional silencing in facultative heterochromatin in a fungal pathogen.
复制标题
DOI：
10.1371/journal.pgen.1010945
复制
发表时间：
2023-09
期刊：
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
--
作者：
兼性异染色质控制许多真核生物的发育和分化。在后生动物、植物和许多丝状真菌中，兼性异染色质的特征在于转录抑制和富集在组蛋白H3赖氨酸27（H3K27me3）处三甲基化的核小体。虽然在许多物种中H3K27me3的丢失导致转录基因沉默的去抑制，但在富含H3K27me3的染色体区域中，额外的上游和下游调节层对于介导转录控制是必要的。在这里，我们研究了组蛋白H4，即H4K20me3，在真菌Zymoseptoria trivetoria，一个全球重要的小麦病原体的组蛋白标记的影响。缺失kmt5（编码唯一负责H4K20甲基化的甲基转移酶的基因）导致转录的整体去抑制，特别是在兼性异染色质区域。在没有H4K20me3的情况下，去阻遏不仅影响已知的基因，而且还影响了大量的新的，以前未检测到的转录本产生的兼性异染色质的辅助染色体上的区域。kmt5缺失株的转录激活伴随着Ash1介导的H3K36me3的完全丧失和影响H3K27me3和H3K4me2分布在兼性异染色质区域的染色质重组。Z.组蛋白H4基因H4K20L、M或Q突变株。三磷酸腺苷重现了这些染色质变化，表明H4K20me3对Ash1介导的H3K36me3很重要。我们获得的突变体的pkmt5比野生型更敏感的遗传毒性压力，pkmt5和pkash1，显示出极大的增加率的辅助染色体丢失。两者合计，我们的研究结果提供了一个意想不到的机制参与兼性异染色质的组装和维护的见解。兼性异染色质包含对特定发育或生命周期阶段重要的基因。这些基因的转录调控受染色质结构的影响。在这里，我们报告，三甲基化赖氨酸20组蛋白H4（H4K20me3），富含兼性异染色质和重要的转录抑制在这些地区的一个重要的农业病原体。此外，正常水平的H4K20me3对于另一种抑制性组蛋白标记Ash1介导的H3K36me3的沉积是必不可少的，并影响包括H3K27me3在内的其他标记的分布。我们对真菌中的H4K20三甲基化水平进行了全基因组评估，我们的发现揭示了建立转录沉默需要多种染色质修饰，为理解这些组蛋白标记之间的上位性关系提供了框架。
Facultative heterochromatin controls development and differentiation in many eukaryotes. In metazoans, plants, and many filamentous fungi, facultative heterochromatin is characterized by transcriptional repression and enrichment with nucleosomes that are trimethylated at histone H3 lysine 27 (H3K27me3). While loss of H3K27me3 results in derepression of transcriptional gene silencing in many species, additional up- and downstream layers of regulation are necessary to mediate control of transcription in chromosome regions enriched with H3K27me3. Here, we investigated the effects of one histone mark on histone H4, namely H4K20me3, in the fungus Zymoseptoria tritici, a globally important pathogen of wheat. Deletion of kmt5, the gene encoding the sole methyltransferase responsible for H4K20 methylation, resulted in global derepression of transcription, especially in regions of facultative heterochromatin. Derepression in the absence of H4K20me3 not only affected known genes but also a large number of novel, previously undetected transcripts generated from regions of facultative heterochromatin on accessory chromosomes. Transcriptional activation in kmt5 deletion strains was accompanied by a complete loss of Ash1-mediated H3K36me3 and chromatin reorganization affecting H3K27me3 and H3K4me2 distribution in regions of facultative heterochromatin. Strains with H4K20L, M or Q mutations in the single histone H4 gene of Z. tritici recapitulated these chromatin changes, suggesting that H4K20me3 is important for Ash1-mediated H3K36me3. The ∆kmt5 mutants we obtained were more sensitive to genotoxic stressors than wild type and both, ∆kmt5 and ∆ash1, showed greatly increased rates of accessory chromosome loss. Taken together, our results provide insights into an unsuspected mechanism involved in the assembly and maintenance of facultative heterochromatin. Facultative heterochromatin contains genes important for specific developmental or life cycle stages. Transcriptional regulation of these genes is influenced by chromatin structure. Here, we report that trimethylation of lysine 20 on histone H4 (H4K20me3), is enriched in facultative heterochromatin and important for transcriptional repression in these regions in an important agricultural pathogen. Furthermore, normal levels of H4K20me3 are essential for deposition of another repressive histone mark, Ash1-mediated H3K36me3, and affect the distribution of other marks including H3K27me3. We conducted a genome-wide assessment of H4K20 trimethylation levels in a fungus, and our discoveries reveal that multiple chromatin modifications are required to establish transcriptional silencing, providing the framework to understand epistasis relationships among these histone marks.