Initiation of Parental Genome Reprogramming in Fertilized Oocyte by Splicing Kinase SRPK1-Catalyzed Protamine
Lan-TaoGou, Do-Hwan Lim, Wubin Ma, Brandon E.Aubol, Yajing Hao, Xin Wang, Jun Zhao, Zhengyu Liang, Changwei Shao, Xuan Zhang, Fan Meng, Hairi Li, Xiaorong Zhang, Ruiming Xu, Dangsheng Li, Michael G.Rosenfeld, Pamela L.Mellon, Joseph A.Adams, Xiang-Dong Fu
Summary
The paternal genome undergoes a massive exchange of histone with protamine for compaction into sperm during spermiogenesis. Upon fertilization, this process is potently reversed, which is essential for parental genome reprogramming and subsequent activation; however, it remains poorly understood how this fundamental process is initiated and regulated. Here, we report that the previously characterized splicing kinase SRPK1 initiates this life-beginning event by catalyzing site-specific phosphorylation of protamine, thereby triggering protamine-to-histone exchange in the fertilized oocyte. Interestingly, protamine undergoes a DNA-dependent phase transition to gel-like condensates and SRPK1-mediated phosphorylation likely helps open up such structures to enhance protamine dismissal by nucleoplasmin (NPM2) and enable the recruitment of HIRA for H3.3 deposition. Remarkably, genome-wide assay for transposase-accessible chromatin sequencing (ATAC-seq) analysis reveals that selective chromatin accessibility in both sperm and MII oocytes is largely erased in early pronuclei in a protamine phosphorylation-dependent manner, suggesting that SRPK1-catalyzed phosphorylation initiates a highly synchronized reorganization program in both parental genomes.
文章链接：https://www.sciencedirect.com/science/article/pii/S0092867420301641?via%3Dihub
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