中国科学院天津工业生物技术研究所Chaoguang Tian等研究人员合作发现，基于CRISPR/dCas9的可编程表观遗传编辑系统可实现基因座靶向组蛋白瓜氨酸化和精确转录调控。相关论文于2024年6月6日在线发表在《遗传学报》上。

据悉，组蛋白瓜氨酸化是由肽基精氨酸脱氨酶介导的一种重要的翻译后修饰，对许多生理过程和表观遗传调控至关重要。然而，组蛋白瓜氨酸化与特定基因调控之间的因果关系仍未解决。

附：英文原文

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

Author: Lang Rao a, Chaoguang Tian a

Issue&Volume: 2024/06/06

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 PPAD from Porphyromonas gingivalis with dCas9. With the assistance of gRNA, PPAD-dCas9 can recruit peptidyl arginine deiminases to specific genomic loci, enabling direct manipulation of the epigenetic landscape and regulation of gene expression. Our citrullination editor allows for site-specific manipulation of histone H3R2,8,17 and 26 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.

DOI: 10.1016/j.jgg.2024.05.010

Source: https://www.sciencedirect.com/science/article/pii/S1673852724001231