title: Meioc maintains an extended meiotic prophase I in mice.
abstract: The meiosis-specific chromosomal events of homolog pairing, synapsis, and recombination occur over an extended meiotic prophase I that is many times longer than prophase of mitosis. Here we show that, in mice, maintenance of an extended meiotic prophase I requires the gene Meioc, a germ-cell specific factor conserved in most metazoans. In mice, Meioc is expressed in male and female germ cells upon initiation of and throughout meiotic prophase I. Mouse germ cells lacking Meioc initiate meiosis: they undergo pre-meiotic DNA replication, they express proteins involved in synapsis and recombination, and a subset of cells progress as far as the zygotene stage of prophase I. However, cells in early meiotic prophase-as early as the preleptotene stage-proceed to condense their chromosomes and assemble a spindle, as if having progressed to metaphase. Meioc-deficient spermatocytes that have initiated synapsis mis-express CYCLIN A2, which is normally expressed in mitotic spermatogonia, suggesting a failure to properly transition to a meiotic cell cycle program. MEIOC interacts with YTHDC2, and the two proteins pull-down an overlapping set of mitosis-associated transcripts. We conclude that when the meiotic chromosomal program is initiated, Meioc is simultaneously induced so as to extend meiotic prophase. Specifically, MEIOC, together with YTHDC2, promotes a meiotic (as opposed to mitotic) cell cycle program via post-transcriptional control of their target transcripts.
authors.affiliation: Whitehead Institute, Cambridge, MA, United States of America.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, United States of America.
authors.forename: Y Q Shirleen
authors.initials: YQS
authors.lastname: Soh
authors.affiliation: Whitehead Institute, Cambridge, MA, United States of America.
authors.forename: Maria M
authors.identifier: 0000-0001-7800-7120
authors.initials: MM
authors.lastname: Mikedis
authors.affiliation: Whitehead Institute, Cambridge, MA, United States of America.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, United States of America.
authors.forename: Mina
authors.identifier: 0000-0002-3387-8608
authors.initials: M
authors.lastname: Kojima
authors.affiliation: Whitehead Institute, Cambridge, MA, United States of America.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, United States of America.
authors.forename: Alexander K
authors.initials: AK
authors.lastname: Godfrey
authors.affiliation: Whitehead Institute, Cambridge, MA, United States of America.
authors.forename: Dirk G
authors.initials: DG
authors.lastname: de Rooij
authors.affiliation: Whitehead Institute, Cambridge, MA, United States of America.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, United States of America.|Howard Hughes Medical Institute, Whitehead Institute, Cambridge, MA, United States of America.
authors.forename: David C
authors.initials: DC
authors.lastname: Page
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D023902:Chromosome Pairing / Q000235:genetics; D056751:Cyclin A2 / Q000096:biosynthesis* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D008938:Mitosis / Q000235:genetics; D011418:Prophase / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D013090:Spermatocytes; D013091:Spermatogenesis / Q000235:genetics; D013093:Spermatogonia / Q000254:growth & development / Q000378:metabolism
chemical_list: C508184:CCNA2 protein, mouse; D018797:Cell Cycle Proteins; D056751:Cyclin A2; C000607599:MEIOC protein, mouse; D016601:RNA-Binding Proteins; C000602643:YTHDF2 protein, mouse