The chromatin remodeler Snf2h is essential for oocyte meiotic cell cycle progression
- Chunxia Zhang1,2,3,8,
- Zhiyuan Chen1,2,3,8,
- Qiangzong Yin1,2,3,
- Xudong Fu1,2,3,
- Yisi Li1,2,3,4,
- Tomas Stopka5,
- Arthur I. Skoultchi5 and
- Yi Zhang1,2,3,6,7
- 1Howard Hughes Medical Institute, Boston Children's Hospital, Boston, Massachusetts 02115, USA;
- 2Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts 02115, USA;
- 3Division of Hematology/Oncology, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts 02115, USA;
- 4Department of Automation, Tsinghua University, Beijing 100084, China;
- 5Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA;
- 6Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA;
- 7Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA
- Corresponding author: yzhang{at}genetics.med.harvard.edu
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↵8 These authors contributed equally to this work.
Abstract
Oocytes are indispensable for mammalian life. Thus, it is important to understand how mature oocytes are generated. As a critical stage of oocytes development, meiosis has been extensively studied, yet how chromatin remodeling contributes to this process is largely unknown. Here, we demonstrate that the ATP-dependent chromatin remodeling factor Snf2h (also known as Smarca5) plays a critical role in regulating meiotic cell cycle progression. Females with oocyte-specific depletion of Snf2h are infertile and oocytes lacking Snf2h fail to undergo meiotic resumption. Mechanistically, depletion of Snf2h results in dysregulation of meiosis-related genes, which causes failure of maturation-promoting factor (MPF) activation. ATAC-seq analysis in oocytes revealed that Snf2h regulates transcription of key meiotic genes, such as Prkar2b, by increasing its promoter chromatin accessibility. Thus, our studies not only demonstrate the importance of Snf2h in oocyte meiotic resumption, but also reveal the mechanism underlying how a chromatin remodeling factor can regulate oocyte meiosis.
Keywords
- chromatin remodeling
- Snf2h
- transcriptional regulation
- germ cell development
- meiotic resumption
- MPF activity
Footnotes
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.331157.119.
- Received July 25, 2019.
- Accepted December 16, 2019.
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