Abstract
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 dCas9.With the assistance of gRNA,PPAD-dCas9 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 ac-curate and efficient tool for exploring gene regulation of histone citrullination.
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