title: Zfy genes are required for efficient meiotic sex chromosome inactivation (MSCI) in spermatocytes.
abstract: During spermatogenesis, germ cells that fail to synapse their chromosomes or fail to undergo meiotic sex chromosome inactivation (MSCI) are eliminated via apoptosis during mid-pachytene. Previous work showed that Y-linked genes Zfy1 and Zfy2 act as 'executioners' for this checkpoint, and that wrongful expression of either gene during pachytene triggers germ cell death. Here, we show that in mice, Zfy genes are also necessary for efficient MSCI and the sex chromosomes are not correctly silenced in Zfy-deficient spermatocytes. This unexpectedly reveals a triple role for Zfy at the mid-pachytene checkpoint in which Zfy genes first promote MSCI, then monitor its progress (since if MSCI is achieved, Zfy genes will be silenced), and finally execute cells with MSCI failure. This potentially constitutes a negative feedback loop governing this critical checkpoint mechanism.
authors.affiliation: Division of Stem Cell Biology and Developmental Genetics, MRC National Institute for Medical Research, Mill Hill, London, UK.|Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch Cedex, France.
authors.forename: Nadège
authors.initials: N
authors.lastname: Vernet
authors.affiliation: Division of Stem Cell Biology and Developmental Genetics, MRC National Institute for Medical Research, Mill Hill, London, UK.|Division of Stem Cell Biology and Developmental Genetics, The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, London, UK.
authors.forename: Shantha K
authors.initials: SK
authors.lastname: Mahadevaiah
authors.affiliation: Reproductive Biology Group, Division of Developmental Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors.forename: Dirk G
authors.initials: DG
authors.lastname: de Rooij
authors.affiliation: Division of Stem Cell Biology and Developmental Genetics, MRC National Institute for Medical Research, Mill Hill, London, UK.|Division of Stem Cell Biology and Developmental Genetics, The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, London, UK.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Burgoyne
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, UK.|School of Biosciences, University of Kent, Canterbury CT2 7NZ, UK.
authors.forename: Peter J I
authors.initials: PJI
authors.lastname: Ellis
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D008297:Male; D008540:Meiosis / Q000235:genetics; D051379:Mice; D013090:Spermatocytes / Q000254:growth & development / Q000378:metabolism*; D013091:Spermatogenesis / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics; D049951:X Chromosome Inactivation / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; C501342:Zfy1 protein, mouse; C501343:Zfy2 protein, mouse