Department of Biochemistry, Jawaharlal Nehru Medical College, Faculty of Medicine, Aligarh Muslim University, Aligarh 202002 India.
Glycobiology. 2021 Sep 20;31(9):1072-1079. doi: 10.1093/glycob/cwab011.
Ever increasing information on genome and proteome has offered fascinating details and new opportunities to understand the molecular biology. It is now known that histone proteins surrounding the DNA play a crucial role in the chromatin structure and function. Histones undergo a plethora of posttranslational enzymatic modifications that influence nucleosome dynamics and affect DNA activity. Earlier research offered insights into the enzymatic modifications of histones; however, attention has been diverted to histone modifications induced by by-products of metabolism without enzymatic engagement in the last decade. Nonenzymatic modifications of histones are believed to be crucial for epigenetic landscape, cellular fate and for role in human diseases. Glycation of histone proteins constitutes the major nonenzymatic modifications of nuclear proteins that have implications in diabetes and cancer. It has emerged that glycation damages nuclear proteins, modifies amino acids of histones at crucial locations, generates adducts affecting histone chromatin interaction, develops neo-epitopes inducing specific immune response and impacts cell function. Presence of circulating antibodies against glycated histone proteins in diabetes and cancer has shown immunological implications with diagnostic relevance. These crucial details make histone glycation an attractive focus for investigators. This review article, therefore, makes an attempt to exclusively summarize the recent research in histone glycation, its impact on structural integrity of chromatin and elaborates on its role in diabetes and cancer. The work offers insights for future scientists who investigate the link between metabolism, biomolecular structures, glycobiology, histone-DNA interactions in relation to diseases in humans.
不断增加的基因组和蛋白质组信息为理解分子生物学提供了引人入胜的细节和新的机会。现在已知，围绕 DNA 的组蛋白在染色质结构和功能中起着至关重要的作用。组蛋白经历了大量的翻译后酶修饰，这些修饰影响核小体的动力学，并影响 DNA 的活性。早期的研究提供了组蛋白酶修饰的见解；然而，在过去十年中，人们的注意力已经转向代谢副产物诱导的组蛋白修饰，而不是酶促参与的组蛋白修饰。组蛋白的非酶修饰被认为对表观遗传景观、细胞命运以及在人类疾病中的作用至关重要。组蛋白蛋白的糖化构成了核蛋白的主要非酶修饰，这些修饰与糖尿病和癌症有关。已经出现的是，糖化损伤核蛋白，在关键位置修饰组蛋白的氨基酸，产生影响组蛋白染色质相互作用的加合物，形成诱导特定免疫反应的新表位，并影响细胞功能。糖尿病和癌症患者循环中针对糖化组蛋白的抗体的存在表明具有免疫相关性和诊断相关性。这些关键细节使组蛋白糖化成为研究人员关注的焦点。因此，本文专门总结了组蛋白糖化的最新研究，阐述了其对染色质结构完整性的影响，并详细说明了其在糖尿病和癌症中的作用。这项工作为未来研究代谢、生物分子结构、糖生物学以及与人类疾病相关的组蛋白-DNA 相互作用之间联系的科学家提供了新的见解。
