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.
摘要：
组蛋白瓜氨酸化，肽基精氨酸脱亚胺酶介导的重要翻译后修饰，对于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。在这项研究中,我们通过将牙龈卟啉单胞菌的肽基精氨酸脱亚胺酶PPAD与dCas9融合，开发了一种可编程的表观遗传学编辑器。在gRNA的帮助下，PPAD-dCas9可以招募肽基精氨酸脱亚胺酶到特定的基因组基因座，能够直接操纵表观遗传景观和调节基因表达。我们的瓜氨酸化编辑器允许对目标人类基因位点的组蛋白H3R2、8、17和26进行位点特异性操作，导致以基因座特异性方式激活或抑制不同的基因。此外，瓜氨酸化编辑器的表观遗传效应是特异性和持续性的.该表观遗传编辑器为探索组蛋白瓜氨酸化的基因调控提供了准确有效的工具。
