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QSER1保护DNA甲基化谷免于从头甲基化
作者:小柯机器人 发布时间:2021/4/11 0:04:02

美国斯隆凯特林研究所Danwei Huangfu、康奈尔医学院Olivier Elemento等研究人员合作发现,QSER1保护DNA甲基化谷免于从头甲基化。相关论文发表在2021年4月9日出版的《科学》杂志上。

通过敲入一个DNA甲基化报告基因,研究人员在人类胚胎干细胞中进行了全基因组CRISPR-Cas9筛选来鉴定DNA甲基化的调节因子。筛选最成功的基因是一个未鉴定的基因QSER1,它被证明是发育基因特别是DNA甲基化谷(或峡谷)中二价启动子和平衡增强子的关键守护者。

研究人员进一步证明了QSER1和TET1的遗传和生化相互作用,并表明它们共同来保护来自DNMT3介导的从头甲基化的转录和发育程序。

据介绍,DNA甲基化对于哺乳动物的发育至关重要,其失调会导致严重的病理状况。负责修饰和去除DNA甲基化的关键酶是已知的,但是它们如何协同调节甲基化仍然是一个核心问题。 

附:英文原文

Title: QSER1 protects DNA methylation valleys from de novo methylation

Author: Gary Dixon, Heng Pan, Dapeng Yang, Bess P. Rosen, Therande Jashari, Nipun Verma, Julian Pulecio, Inbal Caspi, Kihyun Lee, Stephanie Stransky, Abigail Glezer, Chang Liu, Marco Rivas, Ritu Kumar, Yahui Lan, Ingrid Torregroza, Chuan He, Simone Sidoli, Todd Evans, Olivier Elemento, Danwei Huangfu

Issue&Volume: 2021/04/09

Abstract: DNA methylation is essential to mammalian development, and dysregulation can cause serious pathological conditions. Key enzymes responsible for deposition and removal of DNA methylation are known, but how they cooperate to regulate the methylation landscape remains a central question. Using a knockin DNA methylation reporter, we performed a genome-wide CRISPR-Cas9 screen in human embryonic stem cells to discover DNA methylation regulators. The top screen hit was an uncharacterized gene, QSER1, which proved to be a key guardian of bivalent promoters and poised enhancers of developmental genes, especially those residing in DNA methylation valleys (or canyons). We further demonstrate genetic and biochemical interactions of QSER1 and TET1, supporting their cooperation to safeguard transcriptional and developmental programs from DNMT3-mediated de novo methylation.

DOI: 10.1126/science.abd0875

Source: https://science.sciencemag.org/content/372/6538/eabd0875

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037