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一个DNA修复途径可以影响转录噪声从而促进细胞命运的转变
作者:小柯机器人 发布时间:2021/7/25 14:56:12

2021年7月22日,《科学》杂志在线发表了美国科学家的一项最新研究成果。来自加州大学旧金山分校的Leor S. Weinberger小组发现,一个DNA修复途径可以影响转录噪声从而促进细胞命运的转变。

研究人员表明,DNA碱基缺失修复会放大转录噪声,从而促进细胞的重新编程。具体来说,DNA修复蛋白Apex1能识别自然发生的和非自然的碱基修饰,在均衡地维持平均表达水平的同时放大了表达噪声。这种放大的表达噪声源于Apex1介导的DNA超螺旋产生的持续时间较短、强度较高的转录突发。

DNA拓扑结构的重塑首先阻碍了转录,然后加速了转录来维持平均水平。这种机制,被称之为"通过修复的不和谐转录"(DiThR),能促进细胞重编程和分化。这项研究揭示了由DNA碱基修饰介导的转录波动在胚胎发育和疾病中的潜在功能作用。

据悉,基因表达的随机波动("噪声")通常被认为是有害的,但波动也可以用来获得好处。

附:英文原文

Title: A DNA-repair pathway can affect transcriptional noise to promote cell fate transitions

Author: Ravi V. Desai, Xinyue Chen, Benjamin Martin, Sonali Chaturvedi, Dong Woo Hwang, Weihan Li, Chen Yu, Sheng Ding, Matt Thomson, Robert H. Singer, Robert A. Coleman, Maike M.K. Hansen, Leor S. Weinberger

Issue&Volume: 2021/07/22

Abstract: Stochastic fluctuations in gene expression (‘noise’) are often considered detrimental, but fluctuations can also be exploited for benefit (e.g., dither). We show here that DNA base-excision repair amplifies transcriptional noise to facilitate cellular reprogramming. Specifically, the DNA-repair protein Apex1, which recognizes both naturally occurring and unnatural base modifications, amplifies expression noise while homeostatically maintaining mean-expression levels. This amplified expression noise originates from shorter duration, higher intensity, transcriptional bursts generated by Apex1-mediated DNA supercoiling. The remodeling of DNA topology first impedes and then accelerates transcription to maintain mean levels. This mechanism, which we term Discordant Transcription through Repair (DiThR; pronounced /’dither’/), potentiates cellular reprogramming and differentiation. Our study reveals a potential functional role for transcriptional fluctuations mediated by DNA base modifications in embryonic development and disease.

DOI: 10.1126/science.abc6506

Source: https://science.sciencemag.org/content/early/2021/07/21/science.abc6506

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