Pattabiraman Shrivatsav, Baumann Claudia, Guisado Daniela, Eppig John J, Schimenti John C, De La Fuente Rabindranath
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.
Department of Physiology and Pharmacology, University of Georgia College of Veterinary Medicine, Athens, GA 30602.
J Cell Biol. 2015 Jan 5;208(1):53-69. doi: 10.1083/jcb.201404109. Epub 2014 Dec 29.
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.
减数分裂后基因表达对于精子和卵子的发育及成熟至关重要。我们报告称，含双溴结构域蛋白BRWD1对雄性和雌性生育能力均必不可少，它促进单倍体精子细胞特异性转录，但在卵母细胞减数分裂进程中具有不同作用。Brwd1基因缺失导致睾丸中约300个主要为精子细胞特异性的转录本下调，包括几乎完全消除那些编码鱼精蛋白和过渡蛋白的转录本，但与染色质的整体表观遗传变化无关，这表明BRWD1具有选择性作用。在雌性中，Brwd1基因敲除导致严重的染色体浓缩和与端粒结构异常相关的结构缺陷，但在生发泡期基因表达仅有微小变化，包括组蛋白甲基转移酶MLL5和LINE-1元件转座子的表达增加两倍以上。因此，BRWD1功能丧失通过性别二态性机制干扰卵子发生和精子发生的完成：在雌性中，它对于减数分裂染色体稳定性的表观遗传控制至关重要，而在雄性中，它对于减数分裂后精子分化过程中的单倍体基因转录至关重要。
