H3.1K27me1 maintains transcriptional silencing and genome stability by preventing GCN5-mediated histone acetylation.
H3.1K27me1 maintains transcriptional silencing and genome stability by preventing GCN5-mediated histone acetylation.
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DOI：
10.1093/plcell/koaa027
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发表时间：
2021-05-31
期刊：
影响因子：
--
通讯作者：
Jacob Y
中科院分区：
文献类型：
--
作者：
Dong J;LeBlanc C;Poulet A;Mermaz B;Villarino G;Webb KM;Joly V;Mendez J;Voigt P;Jacob Y
表观遗传机制在真核生物基因组稳定性调控中发挥着多种作用。在拟南芥中，H3.1 k27甲基转移酶拟南芥trithorax相关蛋白5 （ATXR5）和ATXR6在DNA复制过程中维持基因组的稳定性，它们催化K27me1在复制依赖性H3.1变异上的沉积。atxr5 - atxr6双突变体中H3.1K27me1的缺失导致异染色质缺陷，包括转录去抑制和基因组不稳定，但涉及的分子机制在很大程度上仍然未知。在这项研究中，我们确定了转录共激活因子和保守的组蛋白乙酰转移酶GCN5在缺乏H3.1K27me1的情况下作为转录去抑制和基因组不稳定的中介。GCN5是植物中saga样复合体的一部分，它需要GCN5相互作用蛋白ADA2b和染色质重塑器CHR6来介导atxr5 - atxr6突变体中的异色缺陷。我们的研究结果还表明，拟南芥GCN5在H3.1变异上乙酰化多个赖氨酸残基，但在H3.1 k27me1缺失的情况下，H3.1 k27和H3.1 k36在诱导基因组不稳定方面发挥重要作用。最后，我们发现GCN5的H3.1K36乙酰化在体外受到H3.1K27me1的负调控。总的来说，这项工作揭示了H3.1K27me1通过限制gcn5介导的组蛋白乙酰化在植物中维持异染色质转录沉默和基因组稳定性中的关键分子作用。
Epigenetic mechanisms play diverse roles in the regulation of genome stability in eukaryotes. In Arabidopsis thaliana, genome stability is maintained during DNA replication by the H3.1K27 methyltransferases ARABIDOPSIS TRITHORAX-RELATED PROTEIN 5 (ATXR5) and ATXR6, which catalyze the deposition of K27me1 on replication-dependent H3.1 variants. Loss of H3.1K27me1 in atxr5 atxr6 double mutants leads to heterochromatin defects, including transcriptional de-repression and genomic instability, but the molecular mechanisms involved remain largely unknown. In this study, we identified the transcriptional co-activator and conserved histone acetyltransferase GCN5 as a mediator of transcriptional de-repression and genomic instability in the absence of H3.1K27me1. GCN5 is part of a SAGA-like complex in plants that requires the GCN5-interacting protein ADA2b and the chromatin remodeler CHR6 to mediate the heterochromatic defects in atxr5 atxr6 mutants. Our results also indicate that Arabidopsis GCN5 acetylates multiple lysine residues on H3.1 variants, but H3.1K27 and H3.1K36 play essential functions in inducing genomic instability in the absence of H3.1K27me1. Finally, we show that H3.1K36 acetylation by GCN5 is negatively regulated by H3.1K27me1 in vitro. Overall, this work reveals a key molecular role for H3.1K27me1 in maintaining transcriptional silencing and genome stability in heterochromatin by restricting GCN5-mediated histone acetylation in plants.
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