ABSTRACT

Histone variants regulate chromatin accessibility and gene transcription. Given their distinct properties and functions, histone varint substitutions allow for profound alteration of nucleosomal architecture and local chromatin landscape. Skeletal myogenesis driven by the key transcription factor MyoD is characterized by precise temporal regulation of myogenic genes. Timed substitution of variants within the nucleosomes provides a powerful means to ensure sequential expression of myogenic genes. Indeed, growing evidence has shown H3.3, H2A.Z, macroH2A, and H1b to be critical for skeletal myogenesis. However, the relative importance of various histone variants and their associated chaperones in myogenesis is not fully appreciated. In this review, we summarize the role that histone variants play in altering chromatin landscape to ensure proper muscle differentiation. The temporal regulation and cross talk between histones variants and their chaperones in conjunction with other forms of epigenetic regulation could be critical to understanding myogenesis and their involvement in myopathies.

摘要

组蛋白变体调节染色质可及性和基因转录。鉴于其独特的特性和功能，组蛋白变体替换允许核小体结构和局部染色质景观的深刻改变。由关键转录因子 MyoD 驱动的骨骼肌生成的特点是生肌基因的精确时间调节。核小体内变体的定时替换提供了一种强有力的手段来确保生肌基因的顺序表达。事实上，越来越多的证据表明 H3.3、H2A.Z、macroH2A 和 H1b 对骨骼肌生成至关重要。然而，各种组蛋白变体及其相关分子伴侣在肌生成中的相对重要性并未得到充分认识。在本次审查中，我们总结了组蛋白变体在改变染色质景观以确保适当的肌肉分化中所起的作用。组蛋白变体及其伴侣之间的时间调节和串扰以及其他形式的表观遗传调节对于理解肌发生及其参与肌病可能至关重要。