ZFP541 and KCTD19 regulate chromatin organization and transcription programs for male meiotic progression

Author:

Zhou Xu1,Fang Kailun2,Liu Yanlei3,Li Weidong1,Tan Yingjin1,Zhang Jiaming3,Yu Xiaoxia3,Wang Guoqiang1,Zhang Yanan3,Shang Yongliang1,Zhang Liangran14ORCID,Chen Charlie Degui2,Wang Shunxin356

Affiliation:

1. Advanced Medical Research Institute Shandong University Jinan Shandong China

2. State 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 Shanghai China

3. State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine Shandong University Jinan Shandong China

4. Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences Shandong Normal University Jinan Shandong China

5. Key Laboratory of Reproductive Endocrinology of Ministry of Education, National Research Center for Assisted Reproductive Technology and Reproductive Genetics Shandong University Jinan Shandong China

6. Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Clinical Research Center for Reproductive Health Shandong Technology Innovation Center for Reproductive Health Jinan Shandong China

Abstract

AbstractThe successful progression of meiosis prophase I requires integrating information from the structural and molecular levels. In this study, we show that ZFP541 and KCTD19 work in the same genetic pathway to regulate the progression of male meiosis and thus fertility. The Zfp541 and/or Kctd19 knockout male mice show various structural and recombination defects including detached chromosome ends, aberrant localization of chromosome axis components and recombination proteins, and globally altered histone modifications. Further analyses on RNA‐seq, ChIP‐seq, and ATAC‐seq data provide molecular evidence for the above defects and reveal that ZFP541/KCTD19 activates the expression of many genes by repressing several major transcription repressors. More importantly, we reveal an unexpected role of ZFP541/KCTD19 in directly modulating chromatin organization. These results suggest that ZFP541/KCTD19 simultaneously regulates the transcription cascade and chromatin organization to ensure the coordinated progression of multiple events at chromosome structural and biochemical levels during meiosis prophase I.

Funder

National Key Research and Development Program of China

National Natural Science Foundation of China

Publisher

Wiley

Subject

Cell Biology,General Medicine

Reference80 articles.

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