Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, 769008, India.
Cell Mol Life Sci. 2014 Sep;71(18):3439-63. doi: 10.1007/s00018-014-1605-4. Epub 2014 Mar 28.
The dynamic nature of chromatin and its myriad modifications play a crucial role in gene regulation (expression and repression) during development, cellular survival, homeostasis, ageing, and apoptosis/death. Histone 3 lysine 4 methylation (H3K4 methylation) catalyzed by H3K4 specific histone methyltransferases is one of the more critical chromatin modifications that is generally associated with gene activation. Additionally, the deposition of H3 variant(s) in conjunction with H3K4 methylation generates an intricately reliable epigenetic regulatory circuit that guides transcriptional activity in normal development and homeostasis. Consequently, alterations in this epigenetic circuit may trigger disease development. The mechanistic relationship between H3 variant deposition and H3K4 methylation during normal development has remained foggy. However, recent investigations in the field of chromatin dynamics in various model organisms, tumors, cancer tissues, and cell lines cultured without and with therapeutic agents, as well as from model reconstituted chromatins reveal that there may be different subsets of chromatin assemblage with specific patterns of histone replacement executing similar functions. In this light, we attempt to explain the intricate control system that maintains chromatin structure and dynamics during normal development as well as during tumor development and cancer progression in this review. Our focus is to highlight the contribution of H3K4 methylation-histone variant crosstalk in regulating chromatin architecture and subsequently its function.
染色质的动态性质及其众多修饰在基因调控（表达和抑制）中起着至关重要的作用，包括发育、细胞存活、内稳态、衰老以及细胞凋亡/死亡。由 H3K4 特异性组蛋白甲基转移酶催化的组蛋白 3 赖氨酸 4 甲基化 (H3K4 methylation) 是更关键的染色质修饰之一，通常与基因激活相关。此外，H3 变体的沉积与 H3K4 甲基化相结合，生成了一个错综复杂的可靠表观遗传调控回路，指导正常发育和内稳态中的转录活性。因此，该表观遗传回路的改变可能会引发疾病的发展。在正常发育过程中，H3 变体沉积与 H3K4 甲基化之间的机制关系仍然模糊不清。然而，最近在各种模式生物、肿瘤、癌组织和无治疗剂及有治疗剂培养的细胞系中的染色质动力学领域的研究表明，可能存在具有特定组蛋白替换模式的不同子集的染色质组装体，执行相似的功能。有鉴于此，我们试图在本综述中解释在正常发育以及肿瘤发生和癌症进展过程中维持染色质结构和动力学的复杂控制系统。我们的重点是强调 H3K4 甲基化-组蛋白变体相互作用在调节染色质结构及其功能方面的贡献。
