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

Yushan Li; Ranran Meng; Shanze Li; Bowen Gu; Xiaotong Xu; Haihang Zhang; Xinshui Tan; Tianyu Shao; Jiawen Wang; Dan Xu; Fengchao Wang

doi:10.1016/j.jgg.2022.03.005

Volume 49 Issue 11

Nov. 2022

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Article Navigation > Journal of Genetics and Genomics > 2022 > 49(11): 1029-1041

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

doi: 10.1016/j.jgg.2022.03.005

a. The School of Public Health, Xinxiang Medical University, Xinxiang, Henan 453003, China;
b. College of Life Sciences, Beijing Normal University, Beijing 100875, China;
c. National Institute of Biological Sciences Beijing, Beijing 102206, China;
d. Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing 100084, China

Funds:

and Xinxiang Medical University (XYBSKYZZ201802). We would like to thank Yanna Sun and Yue Yin for help with the RNA-seq experiment. We would like to thank Jinmei Chen and Yuting Guo for assistance with flow cytometry purification of mouse spermatocytes. We thank Hui Han for mass spectrometry and data analysis.

This work was supported by the National Natural Science Foundation of China (81901537)

the Key Technologies Research and Development Program of Henan Province (192102310131)

Received Date: 2021-12-13
Accepted Date: 2022-03-11
Rev Recd Date: 2022-03-11
Publish Date: 2022-03-25

Abstract

Abstract

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.
- ZFP541,
- KCTD19,
- HDAC1,
- Pachytene progression,
- Meiosis,
- Male fertility

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References(50)

References

Abe, H., Alavattam, K.G., Hu, Y.C., Pang, Q., Andreassen, P.R., Hegde, R.S., Namekawa, S.H., 2020. The initiation of meiotic sex chromosome inactivation sequesters DNA damage signaling from autosomes in mouse spermatogenesis. Curr. Biol. 30, 408-420 e405

Bastos, H., Lassalle, B., Chicheportiche, A., Riou, L., Testart, J., Allemand, I., Fouchet, P., 2005. Flow cytometric characterization of viable meiotic and postmeiotic cells by Hoechst 33342 in mouse spermatogenesis. Cytometry A. 65, 40-49

Bellve, A.R., Cavicchia, J.C., Millette, C.F., O'Brien, D.A., Bhatnagar, Y.M., Dym, M., 1977. Spermatogenic cells of the prepuberal mouse. Isolation and morphological characterization. J. Cell Biol. 74, 68-85

Blanco-Rodriguez, J., 2009. gammaH2AX marks the main events of the spermatogenic process. Microsc. Res. Tech. 72, 823-832

Bolcun-Filas, E., Handel, M.A., 2018. Meiosis: the chromosomal foundation of reproduction. Biol. Reprod. 99, 112-126

Borner, G.V., Kleckner, N., Hunter, N., 2004. Crossover/noncrossover differentiation, synaptonemal complex formation, and regulatory surveillance at the leptotene/zygotene transition of meiosis. Cell. 117, 29-45

Burgoyne, P.S., Mahadevaiah, S.K., Turner, J.M., 2007. The management of DNA double-strand breaks in mitotic G2, and in mammalian meiosis viewed from a mitotic G2 perspective. Bioessays. 29, 974-986

Burgoyne, P.S., Mahadevaiah, S.K., Turner, J.M., 2009. The consequences of asynapsis for mammalian meiosis. Nat. Rev. Genet. 10, 207-216

Chen, H., Lisby, M., Symington, L.S., 2013. RPA coordinates DNA end resection and prevents formation of DNA hairpins. Mol. Cell. 50, 589-600

Chen, Y., Zheng, Y., Gao, Y., Lin, Z., Yang, S., Wang, T., Wang, Q., Xie, N., Hua, R., Liu, M., et al., 2018. Single-cell RNA-seq uncovers dynamic processes and critical regulators in mouse spermatogenesis. Cell Res. 28, 879-896

Choi, E., Han, C., Park, I., Lee, B., Jin, S., Choi, H., Kim, D.H., Park, Z.Y., Eddy, E.M., Cho, C., 2008. A novel germ cell-specific protein, SHIP1, forms a complex with chromatin remodeling activity during spermatogenesis. J. Biol. Chem. 283, 35283-35294

Dix, D.J., Allen, J.W., Collins, B.W., Mori, C., Nakamura, N., Poorman-Allen, P., Goulding, E.H., Eddy, E.M., 1996. Targeted gene disruption of Hsp70-2 results in failed meiosis, germ cell apoptosis, and male infertility. Proc. Natl. Acad. Sci. U.S.A. 93, 3264-3268

Dix, D.J., Allen, J.W., Collins, B.W., Poorman-Allen, P., Mori, C., Blizard, D.R., Brown, P.R., Goulding, E.H., Strong, B.D., Eddy, E.M., 1997. HSP70-2 is required for desynapsis of synaptonemal complexes during meiotic prophase in juvenile and adult mouse spermatocytes. Development. 124, 4595-4603

Drabent, B., Bode, C., Bramlage, B., Doenecke, D., 1996. Expression of the mouse testicular histone gene H1t during spermatogenesis. Histochem. Cell Biol. 106, 247-251

Gaysinskaya, V., Soh, I.Y., van der Heijden, G.W., Bortvin, A., 2014. Optimized flow cytometry isolation of murine spermatocytes. Cytometry A. 85, 556-565

Gerton, J.L., Hawley, R.S., 2005. Homologous chromosome interactions in meiosis: diversity amidst conservation. Nat. Rev. Genet. 6, 477-487

Goetz, P., Chandley, A.C., Speed, R.M., 1984. Morphological and temporal sequence of meiotic prophase development at puberty in the male mouse. J. Cell Sci. 65, 249-263

Handel, M.A., Schimenti, J.C., 2010. Genetics of mammalian meiosis: regulation, dynamics and impact on fertility. Nat. Rev. Genet. 11, 124-136

Hassig, C.A., Fleischer, T.C., Billin, A.N., Schreiber, S.L., Ayer, D.E., 1997. Histone deacetylase activity is required for full transcriptional repression by mSin3A. Cell. 89, 341-347

Heinzel, T., Lavinsky, R.M., Mullen, T.M., Soderstrom, M., Laherty, C.D., Torchia, J., Yang, W.M., Brard, G., Ngo, S.D., Davie, J.R., et al., 1997. A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression. Nature. 387, 43-48

Hirota, T., Blakeley, P., Sangrithi, M.N., Mahadevaiah, S.K., Encheva, V., Snijders, A.P., ElInati, E., Ojarikre, O.A., de Rooij, D.G., Niakan, K.K., et al., 2018. SETDB1 links the meiotic DNA damage response to sex chromosome silencing in mice. Dev. Cell 47, 645-659 e646

Horisawa-Takada, Y., Kodera, C., Takemoto, K., Sakashita, A., Horisawa, K., Maeda, R., Shimada, R., Usuki, S., Fujimura, S., Tani, N., et al., 2021. Meiosis-specific ZFP541 repressor complex promotes developmental progression of meiotic prophase towards completion during mouse spermatogenesis. Nat. Commun. 12, 3184

Hunter, N., 2015. Meiotic recombination: the essence of heredity. Cold Spring Harbor Perspect. Biol. 7

Jacob, C., Christen, C.N., Pereira, J.A., Somandin, C., Baggiolini, A., Lotscher, P., Ozcelik, M., Tricaud, N., Meijer, D., Yamaguchi, T., et al., 2011. HDAC1 and HDAC2 control the transcriptional program of myelination and the survival of Schwann cells. Nat. Neurosci. 14, 429-436

Kaya-Okur, H.S., Wu, S.J., Codomo, C.A., Pledger, E.S., Bryson, T.D., Henikoff, J.G., Ahmad, K., Henikoff, S., 2019. CUT&Tag for efficient epigenomic profiling of small samples and single cells. Nat. Commun. 10, 1930

Keeney, S., Giroux, C.N., Kleckner, N., 1997. Meiosis-specific DNA double-strand breaks are catalyzed by Spo11, a member of a widely conserved protein family. Cell. 88, 375-384

Kelly, R.D., Cowley, S.M., 2013. The physiological roles of histone deacetylase (HDAC) 1 and 2: complex co-stars with multiple leading parts. Biochem. Soc. Trans. 41, 741-749

Kleckner, N., 1996. Meiosis: how could it work? Proc. Natl. Acad. Sci. U.S.A. 93, 8167-8174

Kluin, P.M., Kramer, M.F., de Rooij, D.G., 1982. Spermatogenesis in the immature mouse proceeds faster than in the adult. Int. J. Androl. 5, 282-294

Kohl, K.P., Sekelsky, J., 2013. Meiotic and mitotic recombination in meiosis. Genetics. 194, 327-334

Li, M., Zheng, J., Li, G., Lin, Z., Li, D., Liu, D., Feng, H., Cao, D., Ng, E.H.Y., Li, R.H.W., et al., 2021. The male germline-specific protein MAPS is indispensable for pachynema progression and fertility. Proc. Natl. Acad. Sci. U.S.A. 118

Li, Y.S., Meng, R.R., Chen, X., Shang, C.L., Li, H.B., Zhang, T.J., Long, H.Y., Li, H.Q., Wang, Y.J., Wang, F.C., 2019. Generation of H11-albumin-rtTA transgenic mice: a tool for inducible gene expression in the liver. G3 (Bethesda). 9, 591-599

Liu, Y.J., Liu, C., Chang, Z., Wadas, B., Brower, C.S., Song, Z.H., Xu, Z.L., Shang, Y.L., Liu, W.X., Wang, L.N., et al., 2016. Degradation of the separase-cleaved Rec8, a meiotic cohesin subunit, by the N-end rule pathway. J. Biol. Chem. 291, 7426-7438

Millard, C.J., Watson, P.J., Fairall, L., Schwabe, J.W.R., 2017. Targeting class I histone deacetylases in a "complex" environment. Trends Pharmacol. Sci. 38, 363-377

Mondal, B., Jin, H., Kallappagoudar, S., Sedkov, Y., Martinez, T., Sentmanat, M.F., Poet, G.J., Li, C., Fan, Y., Pruett-Miller, S.M., et al., 2020. The histone deacetylase complex MiDAC regulates a neurodevelopmental gene expression program to control neurite outgrowth. Elife. 9

Nagy, L., Kao, H.Y., Chakravarti, D., Lin, R.J., Hassig, C.A., Ayer, D.E., Schreiber, S.L., Evans, R.M., 1997. Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase. Cell. 89, 373-380

Neale, M.J., Keeney, S., 2006. Clarifying the mechanics of DNA strand exchange in meiotic recombination. Nature. 442, 153-158

Oura, S., Koyano, T., Kodera, C., Horisawa-Takada, Y., Matsuyama, M., Ishiguro, K.I., Ikawa, M., 2021. KCTD19 and its associated protein ZFP541 are independently essential for meiosis in male mice. PLoS Genet. 17, e1009412

Page, J., de la Fuente, R., Manterola, M., Parra, M.T., Viera, A., Berrios, S., Fernandez-Donoso, R., Rufas, J.S., 2012. Inactivation or non-reactivation: what accounts better for the silence of sex chromosomes during mammalian male meiosis? Chromosoma. 121, 307-326

Peters, A.H., Plug, A.W., van Vugt, M.J., de Boer, P., 1997. A drying-down technique for the spreading of mammalian meiocytes from the male and female germline. Chromosome Res. 5, 66-68

Royo, H., Polikiewicz, G., Mahadevaiah, S.K., Prosser, H., Mitchell, M., Bradley, A., de Rooij, D.G., Burgoyne, P.S., Turner, J.M., 2010. Evidence that meiotic sex chromosome inactivation is essential for male fertility. Curr. Biol. 20, 2117-2123

Schmekel, K., Daneholt, B., 1995. The central region of the synaptonemal complex revealed in three dimensions. Trends Cell Biol. 5, 239-242

Shi, B., Xue, J., Zhou, J., Kasowitz, S.D., Zhang, Y., Liang, G., Guan, Y., Shi, Q., Liu, M., Sha, J., et al., 2018. MORC2B is essential for meiotic progression and fertility. PLoS Genet. 14, e1007175

Shinohara, A., Ogawa, H., Ogawa, T., 1992. Rad51 protein involved in repair and recombination in S. cerevisiae is a RecA-like protein. Cell. 69, 457-470

Tarsounas, M., Morita, T., Pearlman, R.E., Moens, P.B., 1999. RAD51 and DMC1 form mixed complexes associated with mouse meiotic chromosome cores and synaptonemal complexes. J. Cell Biol. 147, 207-220

Turner, J.M., 2007. Meiotic sex chromosome inactivation. Development. 134, 1823-1831

Vernet, N., Mahadevaiah, S.K., de Rooij, D.G., Burgoyne, P.S., Ellis, P.J.I., 2016. Zfy genes are required for efficient meiotic sex chromosome inactivation (MSCI) in spermatocytes. Hum. Mol. Genet. 25, 5300-5310

Yin, H., Kang, Z., Zhang, Y., Gong, Y., Liu, M., Xue, Y., He, W., Wang, Y., Zhang, S., Xu, Q., et al., 2021. HDAC3 controls male fertility through enzyme-independent transcriptional regulation at the meiotic exit of spermatogenesis. Nucleic Acids Res. 49, 5106-5123

Yoshida, K., Kondoh, G., Matsuda, Y., Habu, T., Nishimune, Y., Morita, T., 1998. The mouse RecA-like gene Dmc1 is required for homologous chromosome synapsis during meiosis. Mol. Cell. 1, 707-718

Zickler, D., Kleckner, N., 1999. Meiotic chromosomes: integrating structure and function. Annu. Rev. Genet. 33, 603-754

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