Anti-BRD3 (full length) polyclonal antibody

By using in silico methods in a previous study, we identified 100 oocyte-specific genes and 150 genes, enriched in the mouse oocyte. Interestingly, approximately half of the oocyte-specific genes tend to cluster on mouse chromosomes as if they have recently duplicated during evolution. In this study, we focused our attention on mouse BRDT, which belongs to a family of four structurally related proteins characterized by two N-terminal bromodomains and one C-terminal extraterminal domain (ET domain), defining the BET family. In mammals, BRD2, -3, and -4 are ubiquitously expressed, whereas BRDT expression was shown to be restricted to the testis. We were interested to know whether there was a correlation between the evolutionary rate and the specificity of expression of these four paralogous genes. First, we show by RT-PCR and in situ hybridization that BRDT is also expressed in mouse oocyte. Moreover, phylogenetic analyses show that the BRDT germ cell-specific orthology group clearly evolves faster than its ubiquitously expressed paralogs BRD2, BRD3, and BRD4. This suggests that there is a relationship between the evolution of these four groups of orthology and their tissue specificity of expression. (c) 2006 Elsevier Inc. All rights reserved.

Myogenic differentiation proceeds through a highly coordinated cascade of gene activation that necessitates epigenomic changes in chromatin structure. Using a screen of small molecule epigenetic probes we identified three compounds which inhibited myogenic differentiation in C2C12 myoblasts; (+)-JQ1, PFI-1, and Bromosporine. These molecules target Bromodomain and Extra Terminal domain (BET) proteins, which are epigenetic readers of acetylated histone lysine tail residues. BETi-mediated anti-myogenic effects were also observed in a model of MYOD1-mediated myogenic conversion of human fibroblasts, and in primary mouse and human myoblasts. All three BET proteins BRD2, BRD3 and BRD4 exhibited distinct and dynamic patterns of protein expression over the course of differentiation without concomitant changes in mRNA levels, suggesting that BET proteins are regulated at the post-transcriptional level. Specific BET protein knockdown by RNA interference revealed that BRD4 was required for myogenic differentiation, whereas BRD3 down-regulation resulted in enhanced myogenic differentiation. ChIP experiments revealed a preferential binding of BRD4 to the Myog promoter during C2C12 myoblast differentiation, co-incident with increased levels of H3K27 acetylation. These results have identified an essential role for BET proteins in the regulation of skeletal myogenesis, and assign distinct functions to BRD3 and BRD4.