On the Hunt for the Histone Code.

IF 6.1 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Molecular & Cellular Proteomics Pub Date : 2024-11-01 DOI:10.1016/j.mcpro.2024.100873
Beatrix M Ueberheide, Sahana Mollah, Benjamin A Garcia
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Abstract

Our genome is not made of naked DNA, but a fiber (chromatin) composed of DNA and proteins packaged into our chromosomes. The basic building block of chromatin is the nucleosome, which has two copies of each of the proteins called histones (H2A, H2B, H3, and H4) wrapped by 146 base pairs of DNA. Regions of our genetic material are found between the more open (euchromatin) and more compact (heterochromatin) regions of the genome that can be variably accessible to the underlying genes. Furthermore, post-translational modifications (PTMs) on histones, such as on H3, are critical for regulating chromatin accessibility and gene expression. While site specific antibodies were the tool of choice for histone PTM analysis in the early days (pre-2000s), enter Don Hunt changing the histone PTM field forever. Don's clever thinking brought new innovative mass spectrometry-based approaches to the epigenetics field. His lab's effort led to the discovery of many new histone modifications and methods to facilitate the detection and quantification of histone PTMs, which are still considered state of the art in the proteomics field today. Due to Don's pioneering work in this area, many labs have been able to jump into the epigenetics field and "Hunt" down their own histone targets. A walkthrough of those early histone years in the Hunt Lab are described by three of us who were fortunate enough to be at the right place, at the right time.

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寻找组蛋白密码
我们的基因组不是由裸露的 DNA 组成的,而是由 DNA 和蛋白质组成的纤维(染色质),包装在染色体中。染色质的基本组成部分是核小体,核小体由 146 个碱基对的 DNA 包裹着,每个核小体有两个被称为组蛋白(H2A、H2B、H3 和 H4)的蛋白质拷贝。我们的遗传物质区域位于基因组中较为开放(外染色质)和较为紧凑(异染色质)的区域之间,这些区域的潜在基因可以不同程度地进入。此外,组蛋白(如 H3)上的翻译后修饰(PTMs)对于调节染色质可及性和基因表达至关重要。虽然在早期(2000 年代以前),位点特异性抗体是组蛋白 PTM 分析的首选工具,但唐-亨特的出现彻底改变了组蛋白 PTM 领域。唐的聪明才智为表观遗传学领域带来了基于质谱的创新方法。在他的实验室的努力下,人们发现了许多新的组蛋白修饰,并找到了便于检测和量化组蛋白 PTM 的方法,这些方法至今仍被认为是蛋白质组学领域最先进的技术。由于唐在这一领域的开创性工作,许多实验室得以进入表观遗传学领域,"猎杀 "自己的组蛋白目标。我们三人有幸在正确的时间、正确的地点见证了亨特实验室早期组蛋白研究的历程。
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来源期刊
Molecular & Cellular Proteomics
Molecular & Cellular Proteomics 生物-生化研究方法
CiteScore
11.50
自引率
4.30%
发文量
131
审稿时长
84 days
期刊介绍: The mission of MCP is to foster the development and applications of proteomics in both basic and translational research. MCP will publish manuscripts that report significant new biological or clinical discoveries underpinned by proteomic observations across all kingdoms of life. Manuscripts must define the biological roles played by the proteins investigated or their mechanisms of action. The journal also emphasizes articles that describe innovative new computational methods and technological advancements that will enable future discoveries. Manuscripts describing such approaches do not have to include a solution to a biological problem, but must demonstrate that the technology works as described, is reproducible and is appropriate to uncover yet unknown protein/proteome function or properties using relevant model systems or publicly available data. Scope: -Fundamental studies in biology, including integrative "omics" studies, that provide mechanistic insights -Novel experimental and computational technologies -Proteogenomic data integration and analysis that enable greater understanding of physiology and disease processes -Pathway and network analyses of signaling that focus on the roles of post-translational modifications -Studies of proteome dynamics and quality controls, and their roles in disease -Studies of evolutionary processes effecting proteome dynamics, quality and regulation -Chemical proteomics, including mechanisms of drug action -Proteomics of the immune system and antigen presentation/recognition -Microbiome proteomics, host-microbe and host-pathogen interactions, and their roles in health and disease -Clinical and translational studies of human diseases -Metabolomics to understand functional connections between genes, proteins and phenotypes
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