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MBD5 and MBD6 couple DNA methylation to gene silencing through the J-domain protein SILENZIO
Science ( IF 44.7 ) Pub Date : 2021-06-25 , DOI: 10.1126/science.abg6130
Lucia Ichino 1, 2 , Brandon A Boone 1, 2 , Luke Strauskulage 3, 4 , C Jake Harris 2 , Gundeep Kaur 5 , Matthew A Gladstone 2 , Maverick Tan 2 , Suhua Feng 2, 6 , Yasaman Jami-Alahmadi 7 , Sascha H Duttke 8 , James A Wohlschlegel 7 , Xiaodong Cheng 5 , Sy Redding 3 , Steven E Jacobsen 1, 2, 6, 9
Affiliation  

DNA methylation is associated with transcriptional repression of eukaryotic genes and transposons, but the downstream mechanism of gene silencing is largely unknown. Here, we describe two Arabidopsis thaliana methyl-CpG–binding domain proteins, MBD5 and MBD6, that are recruited to chromatin by recognition of CG methylation, and redundantly repress a subset of genes and transposons without affecting DNA methylation levels. These methyl readers recruit a J-domain protein, SILENZIO, that acts as a transcriptional repressor in loss-of-function and gain-of-function experiments. J-domain proteins often serve as co-chaperones with HSP70s. Indeed, we found that SILENZIO’s conserved J-domain motif was required for its interaction with HSP70s and for its silencing function. These results uncover an unprecedented role of a molecular chaperone J-domain protein in gene silencing downstream of DNA methylation.



中文翻译:


MBD5 和 MBD6 通过 J 结构域蛋白 SILENZIO 将 DNA 甲基化与基因沉默结合起来



DNA甲基化与真核基因和转座子的转录抑制有关,但基因沉默的下游机制很大程度上未知。在这里,我们描述了两种拟南芥甲基CpG 结合域蛋白 MBD5 和 MBD6,它们通过识别 CG 甲基化而被招募到染色质,并冗余地抑制基因和转座子的子集,而不影响 DNA 甲基化水平。这些甲基读取器招募一种 J 结构域蛋白 SILENZIO,该蛋白在功能丧失和功能获得实验中充当转录抑制因子。 J 结构域蛋白通常充当 HSP70 的共伴侣。事实上,我们发现 SILENZIO 的保守 J 结构域基序是其与 HSP70 相互作用及其沉默功能所必需的。这些结果揭示了分子伴侣 J 结构域蛋白在 DNA 甲基化下游基因沉默中发挥的前所未有的作用。

更新日期:2021-06-25
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