The Biological Significance of Targeting Acetylation-Mediated Gene Regulation for Designing New Mechanistic Tools and Potential Therapeutics.
The Biological Significance of Targeting Acetylation-Mediated Gene Regulation for Designing New Mechanistic Tools and Potential Therapeutics.
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DOI：
10.3390/biom11030455
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发表时间：
2021-03-18
期刊：
影响因子：
5.5
通讯作者：
Mujtaba S
中科院分区：
文献类型：
--
作者：
O'Garro C;Igbineweka L;Ali Z;Mezei M;Mujtaba S
核小体包装和染色质景观之间的分子相互作用调节下游基因的转录编程和生物学结果。一系列表观遗传修饰在形成染色质结构中起着关键作用，染色质结构控制DNA进入转录机器。氨基酸赖氨酸的乙酰化是一种广泛的表观遗传修饰，其用作基因活化的标记，其在应激期间交织细胞稳态的维持和信号传导的调节。乙酰化的生物化学范围从协调参与细胞周期的蛋白质的稳定性和细胞定位到DNA修复和代谢。此外，赖氨酸乙酰转移酶（KAT）调节调控细胞对微生物感染、遗传毒性应激和炎症反应的转录因子的功能。由于它们在许多生物过程中的核心作用，KAT的突变会导致发育和智力挑战以及代谢紊乱。尽管检测乙酰化的工具的可用性，乙酰化介导的细胞过程的机制知识仍然有限。本综述旨在整合KAT功能的分子和结构基础，这将有助于设计高度选择性的工具，以了解KAT的生物学，从而开发新的疾病治疗方法。
The molecular interplay between nucleosomal packaging and the chromatin landscape regulates the transcriptional programming and biological outcomes of downstream genes. An array of epigenetic modifications plays a pivotal role in shaping the chromatin architecture, which controls DNA access to the transcriptional machinery. Acetylation of the amino acid lysine is a widespread epigenetic modification that serves as a marker for gene activation, which intertwines the maintenance of cellular homeostasis and the regulation of signaling during stress. The biochemical horizon of acetylation ranges from orchestrating the stability and cellular localization of proteins that engage in the cell cycle to DNA repair and metabolism. Furthermore, lysine acetyltransferases (KATs) modulate the functions of transcription factors that govern cellular response to microbial infections, genotoxic stress, and inflammation. Due to their central role in many biological processes, mutations in KATs cause developmental and intellectual challenges and metabolic disorders. Despite the availability of tools for detecting acetylation, the mechanistic knowledge of acetylation-mediated cellular processes remains limited. This review aims to integrate molecular and structural bases of KAT functions, which would help design highly selective tools for understanding the biology of KATs toward developing new disease treatments.
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