The zinc-finger protein basonuclin 2 is required for proper mitotic arrest, prevention of premature meiotic initiation and meiotic progression in mouse male germ cells.
Absence of mitosis and meiosis are distinguishing properties of male germ cells during late fetal and early neonatal periods. Repressors of male germ cell meiosis have been identified, but mitotic repressors are largely unknown, and no protein repressing both meiosis and mitosis is known. We demonstrate here that the zinc-finger protein BNC2 is present in male but not in female germ cells. In testis, BNC2 exists as several spliced isoforms and presumably binds to DNA. Within the male germ cell lineage, BNC2 is restricted to prospermatogonia and undifferentiated spermatogonia. Fetal prospermatogonia that lack BNC2 multiply excessively on embryonic day (E)14.5 and reenter the cell cycle prematurely. Mutant prospermatogonia also engage in abnormal meiosis; on E17.5, Bnc2(-/-) prospermatogonia start synthesizing the synaptonemal protein SYCP3, and by the time of birth, many Bnc2(-/-) prospermatogonia have accumulated large amounts of nonfilamentous SYCP3, thus appearing to be blocked at leptonema. Bnc2(-/-) prospermatogonia do not undergo proper male differentiation, as they lack almost all the mRNA for the male-specific methylation protein DNMT3L and have increased levels of mRNAs that encode meiotic proteins, including STRA8. Bnc2(-/-) prospermatogonia can produce spermatogonia, but these enter meiosis prematurely and undergo massive apoptotic death during meiotic prophase. This study identifies BNC2 as a major regulator of male germ stem cells, which is required for repression of meiosis and mitosis in prospermatogonia, and for meiosis progression during spermatogenesis. In view of the extreme evolutionary conservation of BNC2, the findings described here are likely to apply to many species.
['Vanhoutteghem|Amandine|A|', 'Messiaen|Sébastien|S|', 'Hervé|Françoise|F|', 'Delhomme|Brigitte|B|', 'Moison|Delphine|D|', 'Petit|Jean-Maurice|JM|', 'Rouiller-Fabre|Virginie|V|', 'Livera|Gabriel|G|', 'Djian|Philippe|P|']
D000818:Animals D018797:Cell Cycle Proteins D004248:DNA (Cytosine-5-)-Methyltransferases D004268:DNA-Binding Proteins D019084:Fluorescent Antibody Technique, Indirect D007150:Immunohistochemistry D008297:Male D008540:Meiosis D051379:Mice D018345:Mice, Knockout D008938:Mitosis D009687:Nuclear Proteins D020133:Reverse Transcriptase Polymerase Chain Reaction D017423:Sequence Analysis, RNA D013091:Spermatogenesis D013093:Spermatogonia
Mouse BNC2 Spermatogonia Gonocytes Transcription