近日，美国加州大学洛杉矶分校Steven E. Jacobsen及其研究团队发现，MBD5和MBD6通过J域蛋白SILENZIO将DNA甲基化与基因沉默结合。2021年6月3日，国际知名学术期刊《科学》在线发表了这一成果。

研究人员报道了两种拟南芥甲基-CpG 结合域蛋白MBD5和MBD6，它们通过识别CG甲基化被招募到染色质，并在不影响DNA甲基化水平的情况下冗余地抑制一类基因和转座子。这些甲基阅读器招募了一种J结构域蛋白SILENZIO，它在功能丧失和功能获得实验中充当转录抑制因子。J 域蛋白通常作为HSP70的共同伴侣蛋白。事实上，研究人员发现SILENZIO的保守J域基序是其与HSP70相互作用及其沉默功能所必需的。

因此，这些结果揭示了分子伴侣J结构域蛋白在DNA甲基化下游的基因沉默中的新作用。

据了解，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在很大程度上是未知的。

附：英文原文

Title: MBD5 and MBD6 couple DNA methylation to gene silencing through the J-domain protein SILENZIO

Author: Lucia Ichino, Brandon A. Boone, Luke Strauskulage, C. Jake Harris, Gundeep Kaur, Matthew A. Gladstone, Maverick Tan, Suhua Feng, Yasaman Jami-Alahmadi, Sascha H. Duttke, James A. Wohlschlegel, Xiaodong Cheng, Sy Redding, Steven E. Jacobsen

Issue&Volume: 2021/06/03

Abstract: 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 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.

DOI: 10.1126/science.abg6130

Source: https://science.sciencemag.org/content/early/2021/06/02/science.abg6130