染色质
素数(序理论)
表观基因组
基因组编辑
计算生物学
基因组浏览器
背景(考古学)
计算机科学
表观遗传学
生物
遗传学
基因组学
基因组
DNA
DNA甲基化
基因
数学
组合数学
基因表达
古生物学
作者
Xiaoyi Li,Wei Chen,Beth Martin,Diego Calderon,Choli Lee,Junhong Choi,Florence M. Chardon,Troy A. McDiarmid,Hae-Dong Kim,Jean-Benoît Lalanne,Jenny F. Nathans,Jay Shendure
标识
DOI:10.1101/2023.04.12.536587
摘要
Prime editing is a powerful means of introducing precise changes to specific locations in mammalian genomes. However, the widely varying efficiency of prime editing across target sites of interest has limited its adoption in the context of both basic research and clinical settings. Here, we set out to exhaustively characterize the impact of the cis- chromatin environment on prime editing efficiency. Using a newly developed and highly sensitive method for mapping the genomic locations of a randomly integrated "sensor", we identify specific epigenetic features that strongly correlate with the highly variable efficiency of prime editing across different genomic locations. Next, to assess the interaction of trans -acting factors with the cis -chromatin environment, we develop and apply a pooled genetic screening approach with which the impact of knocking down various DNA repair factors on prime editing efficiency can be stratified by cis -chromatin context. Finally, we demonstrate that we can dramatically modulate the efficiency of prime editing through epigenome editing, i.e. altering chromatin state in a locus-specific manner in order to increase or decrease the efficiency of prime editing at a target site. Looking forward, we envision that the insights and tools described here will broaden the range of both basic research and therapeutic contexts in which prime editing is useful.
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