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组蛋白变体:核功能与疾病

Histone variants: nuclear function and disease.

作者信息

Zink Lisa-Maria, Hake Sandra B

机构信息

BioMedical Center, Department of Molecular Biology, LMU Munich, Großhadener Str. 9, 82152 Planegg-Martinsried, Germany.

BioMedical Center, Department of Molecular Biology, LMU Munich, Großhadener Str. 9, 82152 Planegg-Martinsried, Germany; Center for Integrated Protein Science Munich, Butenandtstr. 5-13, 81377 Munich, Germany.

出版信息

Curr Opin Genet Dev. 2016 Apr;37:82-89. doi: 10.1016/j.gde.2015.12.002. Epub 2016 Jan 28.

Abstract

Histone variants have emerged as important contributors to the regulation of chromatin structure and therefore of almost all DNA-based processes. Hence, these specialized proteins play important roles in transcriptional regulation, cell cycle progression, DNA repair, chromatin stability, chromosome segregation and apoptosis. Due to their evident biological significance, it is not surprising that mutations or the deregulation of their expression levels can have severe implications for cellular functions that ultimately might contribute to or even drive disease development, most notably cancer. Besides the histones themselves, their respective chaperone/remodeling complexes needed for precise variant chromatin deposition, are consequently frequent targets in neoplasms and diverse diseases. In this review, we briefly summarize current understanding on the function of human/mammalian histone variants and their regulatory networks and highlight their roles in cancer development.

摘要

组蛋白变体已成为染色质结构调控的重要贡献者,进而对几乎所有基于DNA的过程产生重要影响。因此,这些特殊蛋白质在转录调控、细胞周期进程、DNA修复、染色质稳定性、染色体分离和细胞凋亡中发挥着重要作用。鉴于其明显的生物学意义,毫不奇怪,其突变或表达水平失调会对细胞功能产生严重影响,最终可能导致或甚至推动疾病发展,尤其是癌症。除了组蛋白本身外,其各自用于精确变体染色质沉积所需的伴侣/重塑复合物,因此也经常成为肿瘤和各种疾病的靶点。在本综述中,我们简要总结了目前对人类/哺乳动物组蛋白变体功能及其调控网络的认识,并强调了它们在癌症发展中的作用。

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