Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, 769008, India.
Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, 769008, India.
Exp Cell Res. 2020 Nov 15;396(2):112314. doi: 10.1016/j.yexcr.2020.112314. Epub 2020 Oct 1.
Gene expression is influenced at many layers by a fine-tuned crosstalk between multiple extrinsic signalling pathways and intrinsic regulatory molecules that respond to environmental stimuli. Epigenetic modifiers like DNA methyltransferases, histone modifying enzymes and chromatin remodellers are reported to act as triggering factors in many scenarios by exhibiting their control over most of the cellular processes. These epigenetic players can either directly regulate gene expression or interact with some effector molecules that harmonize the expression of downstream genes. One such epigenetic regulator which exhibits multifaceted regulation over gene expression is KDM5A. It is classically a transcriptional repressor acting as H3K4me3 demethylase, but also is reported to act as an activator in many contexts either by loss of activity due to inhibition manifested by other interacting proteins or by downregulating the negative players of a given physiological process thereby escalating the framework. Through this review, we draw attention to the remarkable modes of functioning laid by KDM5A on transcriptional and translational processes, affecting gene expression during differentiation and development and finally summing up on role in disease causation (Fig. 1). We also shed light on different orthologs of KDM5A and their organism specific roles, along with comparison of the sequence similarity to extrapolate some unanswered questions about this protein.
基因表达受到多种外在信号通路和内在调节分子之间精细相互作用的影响，这些分子可以响应环境刺激。表观遗传修饰物，如 DNA 甲基转移酶、组蛋白修饰酶和染色质重塑酶，被报道在许多情况下作为触发因素发挥作用，它们通过对大多数细胞过程的控制来展示其功能。这些表观遗传调控因子可以直接调节基因表达，也可以与一些效应分子相互作用，从而协调下游基因的表达。KDM5A 就是这样一种具有多种基因表达调控功能的表观遗传调控因子。它经典地作为 H3K4me3 去甲基酶起转录抑制子的作用，但也有报道称，在许多情况下，它可以作为一种激活剂发挥作用，这种作用要么是由于与其他相互作用的蛋白质相互作用而导致其活性丧失，要么是通过下调给定生理过程的负调控因子来增强调控框架。通过这篇综述，我们注意到 KDM5A 在转录和翻译过程中具有显著的作用模式，影响分化和发育过程中的基因表达，并最终总结了它在疾病发生中的作用（图 1）。我们还探讨了 KDM5A 的不同同源物及其在特定生物体中的作用，并比较了序列相似性，以推断出关于这种蛋白质的一些未解决的问题。
