National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
J Genet Genomics. 2013 Jul 20;40(7):355-65. doi: 10.1016/j.jgg.2013.05.001. Epub 2013 May 20.
Eukaryotic genomic DNA is highly packaged into chromatin by histones to fit inside the nucleus. Other than the bulk packaging role of canonical histones with an expression peak at S phase and replication-coupled deposition, different histone variants have evolved distinct regulatory mechanisms for their expression, deposition and functional implications. The diversity of histone variants results in structural plasticity of chromatin and highlights functionally distinct chromosomal domain, which plays critical roles in development from a fertilized egg into a complex organism, as well as in aging and diseases. However, the mechanisms of this fundamental process are poorly understood so far. It is of particular interest to investigate how the variants are incorporated into chromatin and mark specific chromatin states to regulate gene expression, and how they are involved in development and diseases. In this review, we focus on recent progress in studies of epigenetic regulation of three extensively investigated variants including H2A.Z, macroH2A and H3.3, and their functional implications in development and diseases.
真核生物基因组 DNA 被组蛋白高度包装成染色质,以适应细胞核内的空间。除了经典组蛋白在 S 期和复制偶联沉积时表达高峰的大量包装作用外,不同的组蛋白变体已经进化出不同的表达、沉积和功能意义的调节机制。组蛋白变体的多样性导致染色质结构的可塑性,并突出了功能不同的染色体结构域,这些结构域在从受精卵发育成复杂生物体以及衰老和疾病过程中起着关键作用。然而,到目前为止,这一基本过程的机制还知之甚少。特别值得研究的是,变体如何被整合到染色质中,并标记特定的染色质状态以调节基因表达,以及它们如何参与发育和疾病。在这篇综述中,我们重点介绍了最近在 H2A.Z、macroH2A 和 H3.3 这三种广泛研究的变体的表观遗传调控研究方面的进展,以及它们在发育和疾病中的功能意义。