Abo1 is required for the H3K9me2 to H3K9me3 transition in heterochromatin
Abo1 is required for the H3K9me2 to H3K9me3 transition in heterochromatin
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DOI：
10.1038/s41598-020-63209-y
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发表时间：
2020-04-08
影响因子：
4.6
通讯作者：
Durand-Dubief, Mickael
中科院分区：
文献类型：
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作者：
Dong, Wenbo;Oya, Eriko;Durand-Dubief, Mickael
异染色质调节对于基因组稳定性至关重要。已经发现不同的H3 K9甲基化状态，在异染色质形成和沉默中具有不同的作用。然而，如何控制从H3 K9 me 2到H3 K9 me 3的转变仍然不清楚。在这里，我们调查的作用，保守的溴结构域AAA-ATP酶，BTA 1，参与维持全球核小体组织在裂变酵母。我们确定了几个关键因素，涉及异染色质沉默，基因相互作用与H3 K1：组蛋白脱乙酰酶Clr 3，H3 K9甲基转移酶Clr 4，和HP 1同源Swi 6。在30 ℃培养的缺乏H3 K9 me 1的细胞在异染色质中表现出H3 K9 me 2和H3 K9 me 3的不平衡。在abo 1细胞中，与野生型相比，着丝粒组成型异染色质具有增加的H3 K9 me 2但降低的H3 K9 me 3水平。相反，兼性异染色质区域在abo 1中表现出降低的H3 K9 me 2和H3 K9 me 3水平。全基因组分析表明，abo 1细胞在着丝粒和亚端粒中都有沉默缺陷，但在我们的条件下，在异染色质岛的子集中没有。因此，我们的工作揭示了H3 K9 me 1在直接或间接稳定Clr 4募集以允许异染色质中H3 K9 me 2向H3 K9 me 3过渡中的作用。
Heterochromatin regulation is critical for genomic stability. Different H3K9 methylation states have been discovered, with distinct roles in heterochromatin formation and silencing. However, how the transition from H3K9me2 to H3K9me3 is controlled is still unclear. Here, we investigate the role of the conserved bromodomain AAA-ATPase, Abo1, involved in maintaining global nucleosome organisation in fission yeast. We identified several key factors involved in heterochromatin silencing that interact genetically with Abo1: histone deacetylase Clr3, H3K9 methyltransferase Clr4, and HP1 homolog Swi6. Cells lacking Abo1 cultivated at 30 degrees C exhibit an imbalance of H3K9me2 and H3K9me3 in heterochromatin. In abo1 cells, the centromeric constitutive heterochromatin has increased H3K9me2 but decreased H3K9me3 levels compared to wild-type. In contrast, facultative heterochromatin regions exhibit reduced H3K9me2 and H3K9me3 levels in abo1. Genome-wide analysis showed that abo1 cells have silencing defects in both the centromeres and subtelomeres, but not in a subset of heterochromatin islands in our condition. Thus, our work uncovers a role of Abo1 in stabilising directly or indirectly Clr4 recruitment to allow the H3K9me2 to H3K9me3 transition in heterochromatin.