title: Mouse BRWD1 is critical for spermatid postmeiotic transcription and female meiotic chromosome stability.
abstract: Postmeiotic gene expression is essential for development and maturation of sperm and eggs. We report that the dual bromodomain-containing protein BRWD1, which is essential for both male and female fertility, promotes haploid spermatid-specific transcription but has distinct roles in oocyte meiotic progression. Brwd1 deficiency caused down-regulation of ∼300 mostly spermatid-specific transcripts in testis, including nearly complete elimination of those encoding the protamines and transition proteins, but was not associated with global epigenetic changes in chromatin, which suggests that BRWD1 acts selectively. In females, Brwd1 ablation caused severe chromosome condensation and structural defects associated with abnormal telomere structure but only minor changes in gene expression at the germinal vesicle stage, including more than twofold overexpression of the histone methyltransferase MLL5 and LINE-1 elements transposons. Thus, loss of BRWD1 function interferes with the completion of oogenesis and spermatogenesis through sexually dimorphic mechanisms: it is essential in females for epigenetic control of meiotic chromosome stability and in males for haploid gene transcription during postmeiotic sperm differentiation.
authors.affiliation: Department of Biomedical Sciences and Center for Vertebrate Genomics, Cornell University, College of Veterinary Medicine, Ithaca, NY 14853 Department of Biomedical Sciences and Center for Vertebrate Genomics, Cornell University, College of Veterinary Medicine, Ithaca, NY 14853.
authors.forename: Shrivatsav
authors.initials: S
authors.lastname: Pattabiraman
authors.affiliation: Department of Physiology and Pharmacology, University of Georgia College of Veterinary Medicine, Athens, GA 30602.
authors.forename: Claudia
authors.initials: C
authors.lastname: Baumann
authors.affiliation: Department of Biomedical Sciences and Center for Vertebrate Genomics, Cornell University, College of Veterinary Medicine, Ithaca, NY 14853 Department of Biomedical Sciences and Center for Vertebrate Genomics, Cornell University, College of Veterinary Medicine, Ithaca, NY 14853.
authors.forename: Daniela
authors.initials: D
authors.lastname: Guisado
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609.
authors.forename: John J
authors.initials: JJ
authors.lastname: Eppig
authors.affiliation: Department of Biomedical Sciences and Center for Vertebrate Genomics, Cornell University, College of Veterinary Medicine, Ithaca, NY 14853 Department of Biomedical Sciences and Center for Vertebrate Genomics, Cornell University, College of Veterinary Medicine, Ithaca, NY 14853 rfuente@uga.edu jcs92@cornell.edu.
authors.forename: John C
authors.initials: JC
authors.lastname: Schimenti
authors.affiliation: Department of Physiology and Pharmacology, University of Georgia College of Veterinary Medicine, Athens, GA 30602 rfuente@uga.edu jcs92@cornell.edu.
authors.forename: Rabindranath
authors.initials: R
authors.lastname: De La Fuente
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D043171:Chromosomal Instability; D016000:Cluster Analysis; D044127:Epigenesis, Genetic; D005260:Female; D005298:Fertility; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D006238:Haploidy; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D008540:Meiosis; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D009866:Oogenesis; D010641:Phenotype; D012727:Sex Characteristics; D012737:Sex Factors; D013087:Spermatids / Q000378:metabolism*; D013091:Spermatogenesis; D014158:Transcription, Genetic; D014162:Transfection; D000092468:Bromodomain Containing Proteins
chemical_list: D051548:Histone Acetyltransferases; D011495:Histone-Lysine N-Methyltransferase; C562256:BRD1 protein, mouse; D000092468:Bromodomain Containing Proteins; C539231:MLL5 protein, mouse