Chen Jihong, Li Qiao
Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
Front Cell Dev Biol. 2024 May 27;12:1368171. doi: 10.3389/fcell.2024.1368171. eCollection 2024.
HDAC11 is an epigenetic repressor of gene transcription, acting through its deacetylase activity to remove functional acetyl groups from the lysine residues of histones at genomic loci. It has been implicated in the regulation of different immune responses, metabolic activities, as well as cell cycle progression. Recent studies have also shed lights on the impact of HDAC11 on myogenic differentiation and muscle development, indicating that HDAC11 is important for histone deacetylation at the promoters to inhibit transcription of cell cycle related genes, thereby permitting myogenic activation at the onset of myoblast differentiation. Interestingly, the upstream networks of HDAC11 target genes are mainly associated with cell cycle regulators and the acetylation of histones at the HDAC11 target promoters appears to be residue specific. As such, selective inhibition, or activation of HDAC11 presents a potential therapeutic approach for targeting distinct epigenetic pathways in clinical applications.
HDAC11是一种基因转录的表观遗传抑制因子,通过其脱乙酰酶活性作用于基因组位点的组蛋白赖氨酸残基,去除功能性乙酰基团。它参与了不同免疫反应、代谢活动以及细胞周期进程的调控。最近的研究也揭示了HDAC11对肌源性分化和肌肉发育的影响,表明HDAC11对于启动子处的组蛋白去乙酰化以抑制细胞周期相关基因的转录很重要,从而在成肌细胞分化开始时允许肌源性激活。有趣的是,HDAC11靶基因的上游网络主要与细胞周期调节因子相关,并且HDAC11靶启动子处组蛋白的乙酰化似乎具有残基特异性。因此,选择性抑制或激活HDAC11为临床应用中靶向不同表观遗传途径提供了一种潜在的治疗方法。