Billon Pierre, Côté Jacques
Biochim Biophys Acta. 2013 Mar-Apr;1819(3-4):290-302. doi: 10.1016/j.bbagrm.2011.10.004.
Histone variant H2A.Z is essential in higher eukaryotes and has different functions in the cell. Several studies indicate that H2A.Z is found at specific loci in the genome such as regulatory-gene regions, where it poises genes for transcription. Itsdeposition creates chromatin regions with particular structural characteristics which could favor rapid transcription activation. This review focuses on the highly regulated mechanism of H2A.Z deposition in chromatin which is essential for genome integrity. Chaperones escort H2A.Z to large ATP-dependent chromatin remodeling enzymes which are responsible for its deposition/eviction. Over the last ten years, biochemical, genetic and genomic studies helped us understand the precise role of these complexes in this process. It hasbeen suggested that a cooperation occurs between histone acetyltransferase and chromatin remodeling activities to incorporate H2A.Z in chromatin. Its regulated deposition near centromeres and telomeres also shows its implication in chromosomal structure integrity and parallels a role in DNA damage response. Thedynamics of H2A.Z deposition/eviction at specific loci was shown to be critical for genome expression andmaintenance, thus cell fate. Altogether, recent findings reassert the importance of the regulated depositionof this histone variant. This article is part of a Special Issue entitled: Histone chaperones and Chromatin assembly.
组蛋白变体H2A.Z在高等真核生物中至关重要,且在细胞中具有不同功能。多项研究表明,H2A.Z存在于基因组的特定位点,如调控基因区域,在那里它使基因做好转录准备。其沉积会形成具有特定结构特征的染色质区域,这可能有利于快速转录激活。本综述聚焦于H2A.Z在染色质中沉积的高度调控机制,这对基因组完整性至关重要。分子伴侣将H2A.Z引导至大型ATP依赖的染色质重塑酶,这些酶负责其沉积/移除。在过去十年中,生化、遗传和基因组学研究帮助我们了解了这些复合物在这一过程中的精确作用。有人提出,组蛋白乙酰转移酶与染色质重塑活性之间存在协同作用,以将H2A.Z整合到染色质中。其在着丝粒和端粒附近的调控沉积也表明它与染色体结构完整性有关,并在DNA损伤反应中发挥类似作用。H2A.Z在特定位点的沉积/移除动态对基因组表达和维持至关重要,进而对细胞命运也至关重要。总之,最近的研究结果再次强调了这种组蛋白变体调控沉积的重要性。本文是名为“组蛋白分子伴侣与染色质组装”的特刊的一部分。