CNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, France.
CNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, France; Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Research Institute for Science and Engineering, Institute for Medical-oriented Structural Biology, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
Mol Cell. 2017 Apr 6;66(1):89-101.e8. doi: 10.1016/j.molcel.2017.02.025. Epub 2017 Mar 30.
Histone replacement by transition proteins (TPs) and protamines (Prms) constitutes an essential step for the successful production of functional male gametes, yet nothing is known on the underlying functional interplay between histones, TPs, and Prms. Here, by studying spermatogenesis in the absence of a spermatid-specific histone variant, H2A.L.2, we discover a fundamental mechanism involved in the transformation of nucleosomes into nucleoprotamines. H2A.L.2 is synthesized at the same time as TPs and enables their loading onto the nucleosomes. TPs do not displace histones but rather drive the recruitment and processing of Prms, which are themselves responsible for histone eviction. Altogether, the incorporation of H2A.L.2 initiates and orchestrates a series of successive transitional states that ultimately shift to the fully compacted genome of the mature spermatozoa. Hence, the current view of histone-to-nucleoprotamine transition should be revisited and include an additional step with H2A.L.2 assembly prior to the action of TPs and Prms.
过渡蛋白 (TPs) 和鱼精蛋白 (Prms) 取代组蛋白是成功产生功能性精子的一个重要步骤，但目前尚不清楚组蛋白、TPs 和 Prms 之间的潜在功能相互作用。在这里，通过研究缺乏精子特异性组蛋白变体 H2A.L.2 的精发生成，我们发现了一个涉及核小体转化为核精蛋白的基本机制。H2A.L.2 与 TPs 同时合成，并使其能够加载到核小体上。TPs 不会取代组蛋白，而是驱动 Prms 的募集和加工，而 Prms 本身负责组蛋白的驱逐。总的来说，H2A.L.2 的掺入启动并协调了一系列连续的过渡状态，最终转变为成熟精子完全紧凑的基因组。因此，目前对组蛋白到核精蛋白转换的观点应该重新审视，并包括在 TPs 和 Prms 作用之前增加一个带有 H2A.L.2 组装的步骤。
