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Publication : The ZFP541-KCTD19 complex is essential for pachytene progression by activating meiotic genes during mouse spermatogenesis.

First Author  Li Y Year  2022
Journal  J Genet Genomics Volume  49
Issue  11 Pages  1029-1041
PubMed ID  35341968 Mgi Jnum  J:338159
Mgi Id  MGI:7510302 Doi  10.1016/j.jgg.2022.03.005
Citation  Li Y, et al. (2022) The ZFP541-KCTD19 complex is essential for pachytene progression by activating meiotic genes during mouse spermatogenesis. J Genet Genomics 49(11):1029-1041
abstractText  Meiosis is essential for fertility in sexually reproducing species and this sophisticated process has been extensively studied. Notwithstanding these efforts, key factors involved in meiosis have not been fully characterized. In this study, we investigate the regulatory roles of zinc finger protein 541 (ZFP541) and its interacting protein potassium channel tetramerization domain containing 19 (KCTD19) in spermatogenesis. ZFP541 is expressed from leptotene to the round spermatid stage, while the expression of KCTD19 is initiated in pachytene. Depletion of Zfp541 or Kctd19 leads to infertility in male mice and delays progression from early to mid/late pachynema. In addition, Zfp541(-/-) spermatocytes show abnormal programmed DNA double-strand break repair, impaired crossover formation and resolution, and asynapsis of the XY chromosomes. ZFP541 interacts with KCTD19, histone deacetylase 1/2 (HDAC1/2), and deoxynucleotidyl transferase terminal-interacting protein 1 (DNTTIP1). Moreover, ZFP541 binds to and activates the expression of genes involved in meiosis and post-meiosis including Kctd19; in turn, KCTD19 promotes the transcriptional activation activity of ZFP541. Taken together, our studies reveal that the ZFP541/KCTD19 signaling complex, acting as a key transcription regulator, plays an indispensable role in male fertility by regulating pachytene progression.
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