Diegmüller Felix, Leers Jörg, Hake Sandra B
Institute for Genetics, Justus-Liebig-University Giessen, Giessen, Germany.
Institute for Genetics, Justus-Liebig-University Giessen, Giessen, Germany.
J Biol Chem. 2025 Feb;301(2):108154. doi: 10.1016/j.jbc.2025.108154. Epub 2025 Jan 4.
In 2023, the brilliant chromatin biologist C. David Allis passed away leaving a large void in the scientific community and broken hearts in his family and friends. With this review, we want to tribute Dave's enduring inspiration by focusing on the histone variant H2A.Z, a nucleosome component he was the first to discover as hv1 in Tetrahymena. We summarize the latest findings from the past 5 years regarding the mammalian H2A.Z histone, focusing on its deposition and eviction mechanisms, its roles in transcriptional regulation, DNA damage repair, chromatin structure organization, and embryonic development, as well as how its deregulation or mutation(s) of its histone chaperones contribute to disease development. As Dave liked to say 'Every amino acid matters'; the discovery and characterization of functionally different H2A.Z's isoforms, which vary only in three amino acids, prove him-once again-right.
2023年，杰出的染色质生物学家C. 大卫·阿利斯与世长辞，给科学界留下了巨大的空白，也让他的家人和朋友心碎不已。通过这篇综述，我们想通过聚焦组蛋白变体H2A.Z来致敬戴夫（Dave）持久的灵感，他是第一个在四膜虫中发现作为hv1的核小体成分H2A.Z的人。我们总结了过去5年关于哺乳动物H2A.Z组蛋白的最新发现，重点关注其沉积和移除机制、在转录调控、DNA损伤修复、染色质结构组织和胚胎发育中的作用，以及其组蛋白伴侣的失调或突变如何导致疾病发展。正如戴夫喜欢说的“每一个氨基酸都很重要”；功能不同的H2A.Z亚型的发现和表征，它们仅在三个氨基酸上有所不同，再次证明他是正确的。
