임도환 (University of California, San Diego)

한빛사논문

조회3,387

University of California, San Diego

Cell, Available online 12 March 2020 | https://doi.org/10.1016/j.cell.2020.02.020 Initiation of Parental Genome Reprogramming in Fertilized Oocyte by Splicing Kinase SRPK1-Catalyzed Protamine Phosphorylation

Lan-TaoGou^1,9, Do-HwanLim^1,9, WubinMa^2,9, Brandon E.Aubol³, YajingHao¹, XinWang⁴, JunZhao⁵, ZhengyuLiang¹, ChangweiShao¹, XuanZhang¹, FanMeng¹, HairiLi¹, XiaorongZhang⁶, RuimingXu⁶, DangshengLi⁷, Michael G.Rosenfeld², Pamela L.Mellon^5,8, Joseph A.Adams³, Mo-FangLiu⁴, Xiang-DongFu^1,10,*

¹Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA
²Howard Hughes Medical Institute, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
³Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA
⁴State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences-University of Chinese Academy of Sciences, Shanghai 200031, China
⁵Transgenic and Knockout Mouse Core, University of California, San Diego, La Jolla, CA 92093, USA
⁶Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
⁷Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China
⁸Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92093, USA
⁹These authors contributed equally
¹⁰Lead Contact

^*Corresponding author

Abstract

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.

논문정보

형식Research article
게재일2020년 03월 (BRIC 등록일 2020-03-18)
연구진국외 연구진
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