A programmable CRISPR/dCas9-based epigenetic editing system enabling loci-targeted histone citrullination and precise transcription regulation  

作　　者：Xiaoya Zhang Abhisek Bhattacharya Chunxiang Pu Yan Dai Jia Liu Lang Rao Chaoguang Tian 

机构地区：[1]National Technology Innovation Center of Synthetic Biology,Key Laboratory of Engineering Biology for Low-Carbon Manufacturing,Tianjin Institute of Industrial Biotechnology,Chinese Academy of Sciences,Tianjin 300308,China [2]School of Pharmacy,Jilin University,Changchun,Jilin 130012,China [3]Experimental Immunology Branch,National Cancer Institute,National Institutes of Health,Bethesda,MD 20892,USA

出　　处：《Journal of Genetics and Genomics》2024年第12期1485-1493,共9页遗传学报（英文版）

基　　金：funded by the Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(TSBICIP-CXRC-048)。

摘　　要：Histone citrullination,an important post-translational modification mediated by peptidyl arginine deiminases,is essential for many physiological processes and epigenetic regulation.However,the causal relationship between histone citrullination and specific gene regulation remains unresolved.In this study,we develop a programmable epigenetic editor by fusing the peptidyl arginine deiminase(PAD)PPAD from Porphyromonas gingivalis with d Cas9.With the assistance of g RNA,PPAD-d Cas9 can recruit PPADs to specific genomic loci,enabling direct manipulation of the epigenetic landscape and regulation of gene expression.Our citrullination editor allows for the site-specific manipulation of histone H3R2,8,17 and H3R26 at target human gene loci,resulting in the activation or suppression of different genes in a locus-specific manner.Moreover,the epigenetic effects of the citrullination editor are specific and sustained.This epigenetic editor offers an accurate and efficient tool for exploring gene regulation of histone citrullination.

关 键 词：HISTONE CITRULLINATION Epigenetic editor Peptidyl arginine deiminase dCas9 

分 类 号：Q78[生物学—分子生物学]