Polycomb directs timely activation of germline genes in spermatogenesis
- So Maezawa1,2,3,9,
- Kazuteru Hasegawa1,2,3,9,
- Masashi Yukawa3,4,5,
- Akihiko Sakashita1,2,3,
- Kris G. Alavattam1,2,3,
- Paul R. Andreassen3,6,
- Miguel Vidal7,
- Haruhiko Koseki8,
- Artem Barski3,4,5 and
- Satoshi H. Namekawa1,2,3
- 1Division of Reproductive Sciences, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA;
- 2Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA;
- 3Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 49229, USA;
- 4Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA;
- 5Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA;
- 6Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA;
- 7Department of Cellular and Molecular Biology, Centro de Investigaciones Biológicas, 28040 Madrid, Spain;
- 8Developmental Genetics Laboratory, RIKEN Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan
- Corresponding author: satoshi.namekawa{at}cchmc.org
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↵9 These authors contributed equally to this work.
Abstract
During spermatogenesis, a large number of germline genes essential for male fertility are coordinately activated. However, it remains unknown how timely activation of this group of germline genes is accomplished. Here we show that Polycomb-repressive complex 1 (PRC1) directs timely activation of germline genes during spermatogenesis. Inactivation of PRC1 in male germ cells results in the gradual loss of a stem cell population and severe differentiation defects, leading to male infertility. In the stem cell population, RNF2, the dominant catalytic subunit of PRC1, activates transcription of Sall4, which codes for a transcription factor essential for subsequent spermatogenic differentiation. Furthermore, RNF2 and SALL4 together occupy transcription start sites of germline genes in the stem cell population. Once differentiation commences, these germline genes are activated to enable the progression of spermatogenesis. Our study identifies a novel mechanism by which Polycomb directs the developmental process by activating a group of lineage-specific genes.
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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.302000.117.
- Received May 12, 2017.
- Accepted August 21, 2017.
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