The histone variant H3.3 claims its place in the crowded scene of epigenetics.
The histone variant H3.3 claims its place in the crowded scene of epigenetics.
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DOI：
10.18632/aging.101194
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发表时间：
2017-03-10
期刊：
影响因子：
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通讯作者：
Nicotera P
中科院分区：
文献类型：
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作者：
Bano D;Piazzesi A;Salomoni P;Nicotera P
组蛋白是进化上保守的DNA结合蛋白。作为支架分子，它们显著地调节DNA包装进入所有真核细胞的细胞核。作为对接单位，它们影响转录机制的募集，从而建立独特的基因表达模式，最终促进不同的生物学结果。虽然典型组蛋白H3.1和H3.2在DNA复制期间合成和加载，但组蛋白变体H3.3在整个细胞周期中表达并沉积到染色质中。最近的研究结果表明，H3.3取代了非分裂细胞中的大多数典型H3，以时间依赖的方式达到几乎饱和的水平。因此，H3.3掺入和周转代表了衰老过程中染色质景观调节的另一层。在这方面，我们小组和其他人的工作表明，H3.3在整个进化过程中与年龄相关的过程中发挥着重要作用。在这里，我们总结了目前的知识H3.3生物学，并讨论其异常动力学的影响，在建立细胞状态，可能导致人类病理。重要的是，我们回顾了H3.3营业额作为影响衰老和年龄相关过程的表观遗传事件的一部分的重要性。我们得出结论，新出现的证据表明，H3.3是必要的适当的神经元功能和大脑可塑性。
Histones are evolutionarily conserved DNA-binding proteins. As scaffolding molecules, they significantly regulate the DNA packaging into the nucleus of all eukaryotic cells. As docking units, they influence the recruitment of the transcriptional machinery, thus establishing unique gene expression patterns that ultimately promote different biological outcomes. While canonical histones H3.1 and H3.2 are synthetized and loaded during DNA replication, the histone variant H3.3 is expressed and deposited into the chromatin throughout the cell cycle. Recent findings indicate that H3.3 replaces the majority of canonical H3 in non-dividing cells, reaching almost saturation levels in a time-dependent manner. Consequently, H3.3 incorporation and turnover represent an additional layer in the regulation of the chromatin landscape during aging. In this respect, work from our group and others suggest that H3.3 plays an important function in age-related processes throughout evolution. Here, we summarize the current knowledge on H3.3 biology and discuss the implications of its aberrant dynamics in the establishment of cellular states that may lead to human pathology. Critically, we review the importance of H3.3 turnover as part of epigenetic events that influence senescence and age-related processes. We conclude with the emerging evidence that H3.3 is required for proper neuronal function and brain plasticity.