GCNA is a histone binding protein required for spermatogonial stem cell maintenance
Tóm tắt
Recycling and de-novo deposition of histones during DNA replication is a critical challenge faced by eukaryotic cells and is coordinated by histone chaperones. Spermatogenesis is highly regulated sophisticated process necessitating not only histone modification but loading of testis specific histone variants. Here, we show that Germ Cell Nuclear Acidic protein (GCNA), a germ cell specific protein in adult mice, can bind histones and purified GCNA exhibits histone chaperone activity. GCNA associates with the DNA replication machinery and supports progression through S-phase in murine undifferentiated spermatogonia (USGs). Whilst GCNA is dispensable for embryonic germ cell development, it is required for the maintenance of the USG pool and for long-term production of sperm. Our work describes the role of a germ cell specific histone chaperone in USGs maintenance in mice. These findings provide a mechanistic basis for the male infertility observed in patients carrying GCNA mutations.
Từ khóa
Tài liệu tham khảo
Tang, 2016, Specification and epigenetic programming of the human germ line, Nat. Rev. Genet., 17, 585, 10.1038/nrg.2016.88
Griswold, 2016, Spermatogenesis: the commitment to meiosis, Physiol. Rev., 96, 1, 10.1152/physrev.00013.2015
McCulloch, 2008, The fidelity of DNA synthesis by eukaryotic replicative and translesion synthesis polymerases, Cell Res., 18, 148, 10.1038/cr.2008.4
Ransom, 2010, Chaperoning histones during DNA replication and repair, Cell, 140, 183, 10.1016/j.cell.2010.01.004
Franco, 2005, Histone deposition protein Asf1 maintains DNA replisome integrity and interacts with replication factor C, Genes Dev., 19, 1365, 10.1101/gad.1305005
Groth, 2007, Regulation of replication fork progression through histone supply and demand, Science, 318, 1928, 10.1126/science.1148992
Shibahara, 1999, Replication-dependent marking of DNA by PCNA facilitates CAF-1-coupled inheritance of chromatin, Cell, 96, 575, 10.1016/S0092-8674(00)80661-3
Groth, 2005, Human Asf1 regulates the flow of S phase histones during replicational stress, Mol. Cell, 17, 301, 10.1016/j.molcel.2004.12.018
Hoek, 2003, Chromatin assembly factor 1 is essential and couples chromatin assembly to DNA replication in vivo, Proc. Natl. Acad. Sci. U.S.A., 100, 12183, 10.1073/pnas.1635158100
Sanematsu, 2006, Asf1 is required for viability and chromatin assembly during DNA replication in vertebrate cells, J. Biol. Chem., 281, 13817, 10.1074/jbc.M511590200
Schulz, 2006, The histone chaperone ASF1 localizes to active DNA replication forks to mediate efficient DNA replication, FASEB J., 20, 488, 10.1096/fj.05-5020fje
Clemot, 2018, The replicative histone chaperone CAF1 is essential for the maintenance of identity and genome integrity in adult stem cells, Development, 145, 10.1242/dev.161190
Messiaen, 2016, Loss of the histone chaperone ASF1B reduces female reproductive capacity in mice, Reproduction, 151, 477, 10.1530/REP-15-0327
Enders, 1994, Developmentally regulated expression of a mouse germ cell nuclear antigen examined from embryonic day 11 to adult in male and female mice, Dev. Biol., 163, 331, 10.1006/dbio.1994.1152
Tanaka, 1997, A germ cell-specific nuclear antigen recognized by a monoclonal antibody raised against mouse testicular germ cells, Int. J. Androl., 20, 361, 10.1046/j.1365-2605.1998.00080.x
Arafat, 2021, Pathogenic variations in Germ Cell nuclear Acidic peptidase (GCNA) are associated with human male infertility, Eur. J. Hum. Genet., 29, 1781, 10.1038/s41431-021-00946-2
Hardy, 2021, Variants in GCNA, X-linked germ-cell genome integrity gene, identified in men with primary spermatogenic failure, Hum. Genet., 140, 1169, 10.1007/s00439-021-02287-y
Carmell, 2016, A widely employed germ cell marker is an ancient disordered protein with reproductive functions in diverse eukaryotes, Elife, 5, e19993, 10.7554/eLife.19993
Bhargava, 2020, GCNA preserves genome integrity and fertility across species, Dev. Cell, 52, 38, 10.1016/j.devcel.2019.11.007
Dokshin, 2020, GCNA interacts with Spartan and Topoisomerase II to regulate genome stability, Dev. Cell, 52, 53, 10.1016/j.devcel.2019.11.006
Borgermann, 2019, SUMOylation promotes protective responses to DNA-protein crosslinks, EMBO J., 38, e101496, 10.15252/embj.2019101496
Szabo, 2002, Allele-specific expression of imprinted genes in mouse migratory primordial germ cells, Mech. Dev., 115, 157, 10.1016/S0925-4773(02)00087-4
Walker, 2019, Polychromic reporter mice reveal unappreciated innate lymphoid cell progenitor heterogeneity and elusive ILC3 progenitors in bone marrow, Immunity, 51, 104, 10.1016/j.immuni.2019.05.002
Clapcote, 2005, Simplex PCR assay for sex determination in mice, BioTechniques, 38, 702, 10.2144/05385BM05
Hayashi, 2013, Generation of eggs from mouse embryonic stem cells and induced pluripotent stem cells, Nat. Protoc., 8, 1513, 10.1038/nprot.2013.090
Arakawa, 2001, Mutant loxP vectors for selectable marker recycle and conditional knock-outs, BMC Biotechnol., 1, 7, 10.1186/1472-6750-1-7
Sirbu, 2012, Monitoring the spatiotemporal dynamics of proteins at replication forks and in assembled chromatin using isolation of proteins on nascent DNA, Nat. Protoc., 7, 594, 10.1038/nprot.2012.010
Linding, 2003, GlobPlot: exploring protein sequences for globularity and disorder, Nucleic Acids Res., 31, 3701, 10.1093/nar/gkg519
Babicki, 2016, Heatmapper: web-enabled heat mapping for all, Nucleic Acids Res., 44, W147, 10.1093/nar/gkw419
Fang, 2017, Efficient and inexpensive transient expression of multispecific multivalent antibodies in Expi293 cells, Biol. Proced. Online, 19, 11, 10.1186/s12575-017-0060-7
Schindelin, 2012, Fiji: an open-source platform for biological-image analysis, Nat. Methods, 9, 676, 10.1038/nmeth.2019
Buaas, 2004, Plzf is required in adult male germ cells for stem cell self-renewal, Nat Genet, 36, 647, 10.1038/ng1366
Costoya, 2004, Essential role of Plzf in maintenance of spermatogonial stem cells, Nat Genet, 36, 653, 10.1038/ng1367
Liao, 2014, DNMT3L promotes quiescence in postnatal spermatogonial progenitor cells, Development, 141, 2402, 10.1242/dev.105130
Gao, 2006, The Wilms tumor gene, Wt1, is required for Sox9 expression and maintenance of tubular architecture in the developing testis, Proc. Natl. Acad. Sci. U.S.A., 103, 11987, 10.1073/pnas.0600994103
Fu, 2018, PAK1 Promotes the proliferation and inhibits apoptosis of Human spermatogonial stem cells via PDK1/KDR/ZNF367 and ERK1/2 and AKT pathways, Mol. Ther. Nucleic Acids, 12, 769, 10.1016/j.omtn.2018.06.006
Diao, 2016, Alteration of protein prenylation promotes spermatogonial differentiation and exhausts spermatogonial stem cells in newborn mice, Sci. Rep., 6, 28917, 10.1038/srep28917
Shirakawa, 2013, An epigenetic switch is crucial for spermatogonia to exit the undifferentiated state toward a Kit-positive identity, Development, 140, 3565, 10.1242/dev.094045
Takubo, 2008, Stem cell defects in ATM-deficient undifferentiated spermatogonia through DNA damage-induced cell-cycle arrest, Cell Stem Cell, 2, 170, 10.1016/j.stem.2007.10.023
Stingele, 2016, Mechanism and regulation of DNA-protein crosslink repair by the DNA-dependent metalloprotease SPRTN, Mol. Cell, 64, 688, 10.1016/j.molcel.2016.09.031
Stingele, 2017, Mechanisms of DNA-protein crosslink repair, Nat. Rev. Mol. Cell Biol., 18, 563, 10.1038/nrm.2017.56
de Rooij, 2003, Specific arrests of spermatogenesis in genetically modified and mutant mice, Cytogenet. Genome Res., 103, 267, 10.1159/000076812
Barchi, 2005, Surveillance of different recombination defects in mouse spermatocytes yields distinct responses despite elimination at an identical developmental stage, Mol. Cell. Biol., 25, 7203, 10.1128/MCB.25.16.7203-7215.2005
Eickbush, 1978, The histone core complex: an octamer assembled by two sets of protein-protein interactions, Biochemistry, 17, 4955, 10.1021/bi00616a016
Bannister, 2011, Regulation of chromatin by histone modifications, Cell Res., 21, 381, 10.1038/cr.2011.22
Warren, 2017, Fly fishing for histones: catch and release by histone chaperone intrinsically disordered regions and acidic stretches, J. Mol. Biol., 429, 2401, 10.1016/j.jmb.2017.06.005
Kapust, 1999, Escherichia coli maltose-binding protein is uncommonly effective at promoting the solubility of polypeptides to which it is fused, Protein Sci., 8, 1668, 10.1110/ps.8.8.1668
Germond, 1975, Folding of the DNA double helix in chromatin-like structures from simian virus 40, Proc. Natl. Acad. Sci. U.S.A., 72, 1843, 10.1073/pnas.72.5.1843
Sirbu, 2011, Analysis of protein dynamics at active, stalled, and collapsed replication forks, Genes Dev., 25, 1320, 10.1101/gad.2053211
Maddi, 2020, Wss1 Promotes replication stress tolerance by degrading histones, Cell Rep., 30, 3117, 10.1016/j.celrep.2020.02.018
Ahmed, 2020, Chromatin architectural factors as safeguards against excessive supercoiling during DNA replication, Int. J. Mol. Sci., 21, 10.3390/ijms21124504
Hajkova, 2008, Chromatin dynamics during epigenetic reprogramming in the mouse germ line, Nature, 452, 877, 10.1038/nature06714
Seki, 2005, Extensive and orderly reprogramming of genome-wide chromatin modifications associated with specification and early development of germ cells in mice, Dev. Biol., 278, 440, 10.1016/j.ydbio.2004.11.025