To Ub or not to Ub: The epic dilemma of histones that regulate gene expression and epigenetic cross-talk

IF 2.6 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2024-05-13 DOI:10.1016/j.bbagrm.2024.195033

Anirban Dasgupta , Sandhik Nandi , Sayan Gupta , Siddhartha Roy , Chandrima Das

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Abstract

A dynamic array of histone post-translational modifications (PTMs) regulate diverse cellular processes in the eukaryotic chromatin. Among them, histone ubiquitination is particularly complex as it alters nucleosome surface area fostering intricate cross-talk with other chromatin modifications. Ubiquitin signaling profoundly impacts DNA replication, repair, and transcription. Histones can undergo varied extent of ubiquitination such as mono, multi-mono, and polyubiquitination, which brings about distinct cellular fates. Mechanistic studies of the ubiquitin landscape in chromatin have unveiled a fascinating tapestry of events that orchestrate gene regulation. In this review, we summarize the key contributors involved in mediating different histone ubiquitination and deubiquitination events, and discuss their mechanism which impacts cell transcriptional identity and DNA damage response. We also focus on the proteins bearing epigenetic reader modules critical in discerning site-specific histone ubiquitination, pivotal for establishing complex epigenetic crosstalk. Moreover, we highlight the role of histone ubiquitination in different human diseases including neurodevelopmental disorders and cancer. Overall the review elucidates the intricate orchestration of histone ubiquitination impacting diverse cellular functions and disease pathogenesis, and provides insights into the current challenges of targeting them for therapeutic interventions.

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要Ub还是不要Ub？组蛋白调控基因表达和表观遗传学交叉对话的两难困境。

组蛋白的一系列动态翻译后修饰（PTM）调节着真核染色质中的各种细胞过程。其中，组蛋白泛素化尤为复杂，因为它改变了核小体的表面积，促进了与其他染色质修饰之间错综复杂的交叉对话。泛素信号转导对 DNA 复制、修复和转录产生深远影响。组蛋白可以发生不同程度的泛素化，如单泛素化、多泛素化和多泛素化，从而带来不同的细胞命运。对染色质中泛素结构的机理研究揭示了基因调控过程中的一系列引人入胜的事件。在这篇综述中，我们总结了参与介导不同组蛋白泛素化和去泛素化事件的主要贡献者，并讨论了它们影响细胞转录特性和 DNA 损伤反应的机制。我们还重点研究了带有表观遗传阅读器模块的蛋白质，它们对识别特定位点的组蛋白泛素化至关重要，是建立复杂表观遗传串扰的关键。此外，我们还强调了组蛋白泛素化在不同人类疾病（包括神经发育障碍和癌症）中的作用。总之，这篇综述阐明了组蛋白泛素化的复杂协调作用对多种细胞功能和疾病发病机制的影响，并揭示了目前以组蛋白泛素化为靶点进行治疗干预所面临的挑战。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms 生物-生化与分子生物学

CiteScore

9.20

自引率

2.10%

发文量

审稿时长

44 days

期刊介绍： BBA Gene Regulatory Mechanisms includes reports that describe novel insights into mechanisms of transcriptional, post-transcriptional and translational gene regulation. Special emphasis is placed on papers that identify epigenetic mechanisms of gene regulation, including chromatin, modification, and remodeling. This section also encompasses mechanistic studies of regulatory proteins and protein complexes; regulatory or mechanistic aspects of RNA processing; regulation of expression by small RNAs; genomic analysis of gene expression patterns; and modeling of gene regulatory pathways. Papers describing gene promoters, enhancers, silencers or other regulatory DNA regions must incorporate significant functions studies.