- Gou, Lan-Tao;
- Lim, Do-Hwan;
- Ma, Wubin;
- Aubol, Brandon E;
- Hao, Yajing;
- Wang, Xin;
- Zhao, Jun;
- Liang, Zhengyu;
- Shao, Changwei;
- Zhang, Xuan;
- Meng, Fan;
- Li, Hairi;
- Zhang, Xiaorong;
- Xu, Ruiming;
- Li, Dangsheng;
- Rosenfeld, Michael G;
- Mellon, Pamela L;
- Adams, Joseph A;
- Liu, Mo-Fang;
- Fu, Xiang-Dong
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.