title: A-MYB (MYBL1) transcription factor is a master regulator of male meiosis.
abstract: The transcriptional regulation of mammalian meiosis is poorly characterized, owing to few genetic and ex vivo models. From a genetic screen, we identify the transcription factor MYBL1 as a male-specific master regulator of several crucial meiotic processes. Spermatocytes bearing a novel separation-of-function allele (Mybl1(repro9)) had subtle defects in autosome synapsis in pachynema, a high incidence of unsynapsed sex chromosomes, incomplete double-strand break repair on synapsed pachytene chromosomes and a lack of crossing over. MYBL1 protein appears in pachynema, and its mutation caused specific alterations in expression of diverse genes, including some translated postmeiotically. These data, coupled with chromatin immunoprecipitation (ChIP-chip) experiments and bioinformatic analysis of promoters, identified direct targets of MYBL1 regulation. The results reveal that MYBL1 is a master regulator of meiotic genes that are involved in multiple processes in spermatocytes, particularly those required for cell cycle progression through pachynema.
authors.affiliation: Cornell University College of Veterinary Medicine, Department of Biomedical Sciences, Center for Vertebrate Genomics, Ithaca, NY 14850, USA.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Bolcun-Filas
authors.forename: Laura A
authors.initials: LA
authors.lastname: Bannister
authors.forename: Alex
authors.initials: A
authors.lastname: Barash
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Schimenti
authors.forename: Suzanne A
authors.initials: SA
authors.lastname: Hartford
authors.forename: John J
authors.initials: JJ
authors.lastname: Eppig
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Handel
authors.forename: Lishuang
authors.initials: L
authors.lastname: Shen
authors.forename: John C
authors.initials: JC
authors.lastname: Schimenti
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D053903:DNA Breaks, Double-Stranded; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007248:Infertility, Male / Q000235:genetics; D008297:Male; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D008969:Molecular Sequence Data; D009154:Mutation; D049471:Pachytene Stage / Q000502:physiology; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D013090:Spermatocytes / Q000166:cytology / Q000502:physiology*; D013091:Spermatogenesis / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C490283:Mybl1 protein, mouse; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators; D014157:Transcription Factors