![]() (H-I) Brdt-/- spermatocytes exhibit fully synapsed autosomal bivalents, but numerous sex chromosomes are completely unsynapsed (I, inset). In WT early (F) and mid pachynema (G), all chromosomes are fully synapsed, including the sex chromosomes. (F-I) Immunolocalization of SYCP1 (green) and SYCP3 (red). n = 62 and 99 early pachytene, and 125 and 132 mid/ late pachytene WT and Brdt-/- spermatocytes respectively. Samples were obtained from three WT and Brdt-/- 3 month-old mice. (E) Quantification of sex chromosomes with synapsis defects at the PAR in WT (black bar) and Brdt-/- (grey bar) spermatocytes. (B, D) At mid pachynema, γH2AX is observed only in the X and Y chromosomes, including those in complete asynapsis (D, inset). (A, C) In both WT and Brdt-/- early pachytene spermatocytes, γH2AX is present in the sex chromosomes and as foci in the chromatin adjacent to the SC. (A-D) Immunolocalization of γH2AX (green) and SYCP3 (red). A schematic representation of each inset is shown below the original, with the X chromosome represented in purple and the Y chromosome in red. Upper insets show an enlargement of the sex chromosomes. (A-D, F-I) Chromosome spreads of wild type (WT) and Brdt-/- early and mid pachytene spermatocytes. Our observations reveal novel findings about the function of BRDT in meiosis and provide insight into how epigenetic regulators modulate the progression of male mammalian meiosis and the formation of haploid gametes. Furthermore, the homeostasis of crossover formation and localization during pachynema was altered, underlining a possible epigenetic mechanism by which crossovers are regulated and differentially established in mammalian male genomes. We also found that BRDT controls the global chromatin organization and histone modifications of the chromatin attached to the synaptonemal complex. Loss of BRDT function disrupts the epigenetic state of the meiotic sex chromosome inactivation in spermatocytes, affecting the synapsis and silencing of the X and Y chromosomes. Here we report that BRDT is an essential regulator of chromatin organization and reprograming during prophase I of meiosis. Although BRDT has been implicated in chromatin remodeling and mRNA processing during spermiogenesis, little is known about its role in meiotic processes. In contrast, complete loss of BRDT blocks the progression of spermatocytes into the first meiotic division, resulting in a complete absence of post-meiotic cells. Although BRDT is expressed in both spermatocytes and spermatids, loss of the first bromodomain of BRDT leads to severe defects in spermiogenesis without overtly compromising meiosis. ![]() The testis-specific BET member, BRDT, is essential for the normal progression of spermatogenesis as mutations in the Brdt gene result in complete male sterility. The double bromodomain and extra-terminal domain (BET) proteins are critical epigenetic readers that bind to acetylated histones in chromatin and regulate transcriptional activity and modulate changes in chromatin structure and organization. ![]()
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