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Nat. Struct. Mol. Biol., Mar 03 2025, | https://doi.org/10.1038/s41594-025-01509-5
ZBTB16/PLZF regulates juvenile spermatogonial stem cell development through an extensive transcription factor poising network
Chongil Yi 1, Yuka Kitamura 2, So Maezawa 3, Satoshi H. Namekawa 2 & Bradley R. Cairns 1,*
1Howard Hughes Medical Institute, Huntsman Cancer Institute, Department of Oncological Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA.
2Department of Microbiology and Molecular Genetics, University of California, Davis, CA, USA.
3Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Chiba, Japan.
2Department of Microbiology and Molecular Genetics, University of California, Davis, CA, USA.
3Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Chiba, Japan.
*Corresponding author: correspondence to Bradley R. Cairns
Abstract
Spermatogonial stem cells balance self-renewal with differentiation and spermatogenesis to ensure continuous sperm production. Here, we identify roles for the transcription factor zinc finger and BTB domain-containing protein 16 (ZBTB16; also known as promyelocytic leukemia zinc finger (PLZF)) in juvenile mouse undifferentiated spermatogonia (uSPG) in promoting self-renewal and cell-cycle progression to maintain uSPG and transit-amplifying states. Notably, ZBTB16, Spalt-like transcription factor 4 (SALL4) and SRY-box transcription factor 3 (SOX3) colocalize at over 12,000 promoters regulating uSPG and meiosis. These regions largely share broad histone 3 methylation and acetylation (H3K4me3 and H3K27ac), DNA hypomethylation, RNA polymerase II (RNAPol2) and often CCCTC-binding factor (CTCF). Hi-C analyses show robust three-dimensional physical interactions among these cobound promoters, suggesting the existence of a transcription factor and higher-order active chromatin interaction network within uSPG that poises meiotic promoters for subsequent activation. Conversely, these factors do not notably occupy germline-specific promoters driving spermiogenesis, which instead lack promoter-promoter physical interactions and bear DNA hypermethylation, even when active. Overall, ZBTB16 promotes uSPG cell-cycle progression and colocalizes with SALL4, SOX3, CTCF and RNAPol2 to help establish an extensive and interactive chromatin poising network.
논문정보
- Research article
- 2025년 03월 (BRIC 등록일 2025-03-13)
- 국외 연구진
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