Dijkwel Yasmin, Tremethick David J
Transcription and Chromatin Group, Genome Sciences and Cancer Division, The John Curtin School of Medical Research, The Australian National University, Canberra 2601, Australia.
J Dev Biol. 2022 Jul 1;10(3):28. doi: 10.3390/jdb10030028.
During the emergence and radiation of complex multicellular eukaryotes from unicellular ancestors, transcriptional systems evolved by becoming more complex to provide the basis for this morphological diversity. The way eukaryotic genomes are packaged into a highly complex structure, known as chromatin, underpins this evolution of transcriptional regulation. Chromatin structure is controlled by a variety of different epigenetic mechanisms, including the major mechanism for altering the biochemical makeup of the nucleosome by replacing core histones with their variant forms. The histone H2A variant H2A.Z is particularly important in early metazoan development because, without it, embryos cease to develop and die. However, H2A.Z is also required for many differentiation steps beyond the stage that H2A.Z-knockout embryos die. H2A.Z can facilitate the activation and repression of genes that are important for pluripotency and differentiation, and acts through a variety of different molecular mechanisms that depend upon its modification status, its interaction with histone and nonhistone partners, and where it is deposited within the genome. In this review, we discuss the current knowledge about the different mechanisms by which H2A.Z regulates chromatin function at various developmental stages and the chromatin remodeling complexes that determine when and where H2A.Z is deposited.
在复杂多细胞真核生物从单细胞祖先中出现并辐射演化的过程中，转录系统通过变得更加复杂而进化，为这种形态多样性提供了基础。真核生物基因组被包装成一种高度复杂的结构（称为染色质）的方式，支撑了转录调控的这一进化过程。染色质结构受多种不同的表观遗传机制控制，包括通过用其变体形式取代核心组蛋白来改变核小体生化组成的主要机制。组蛋白H2A变体H2A.Z在早期后生动物发育中尤为重要，因为没有它，胚胎就会停止发育并死亡。然而，在H2A.Z基因敲除胚胎死亡阶段之后的许多分化步骤中也需要H2A.Z。H2A.Z可以促进对多能性和分化重要的基因的激活和抑制，并通过多种不同的分子机制起作用，这些机制取决于其修饰状态、与组蛋白和非组蛋白伴侣的相互作用以及它在基因组中的沉积位置。在这篇综述中，我们讨论了目前关于H2A.Z在各个发育阶段调节染色质功能的不同机制以及决定H2A.Z何时何地沉积的染色质重塑复合物的知识。
