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Background  Brd2 belongs to the bromodomain-extraterminal domain (BET) family of transcriptional co-regulators, and functions as a pivotal histone-directed recruitment scaffold in chromatin modification complexes affecting signal-dependent transcription. Brd2 facilitates expression of genes promoting proliferation and is implicated in apoptosis and in egg maturation and meiotic competence in mammals; it is also a susceptibility gene for juvenile myoclonic epilepsy (JME) in humans. The  brd2  ortholog in  Drosophila  is a maternal effect, embryonic lethal gene that regulates several homeotic loci, including Ultrabithorax. Despite its importance, there are few systematic studies of  Brd2  developmental expression in any organism. To help elucidate both conserved and novel gene functions, we cloned and characterized expression of  brd2  cDNAs in zebrafish, a vertebrate system useful for genetic analysis of development and disease, and for study of the evolution of gene families and functional diversity in chordates.    Results  We identify cDNAs representing two paralogous  brd2  loci in zebrafish,  brd2a  on chromosome 19 and  brd2b  on chromosome 16. By sequence similarity, syntenic and phylogenetic analyses, we present evidence for structural divergence of  brd2  after gene duplication in fishes.  brd2  paralogs show potential for modular domain combinations, and exhibit distinct RNA expression patterns throughout development. RNA  in situ  hybridizations in oocytes and embryos implicate  brd2a  and  brd2b  as maternal effect genes involved in egg polarity and egg to embryo transition, and as zygotic genes important for development of the vertebrate nervous system and for morphogenesis and differentiation of the digestive tract. Patterns of  brd2  developmental expression in zebrafish are consistent with its proposed role in  Homeobox  gene regulation.    Conclusion  Expression profiles of zebrafish  brd2  paralogs support a role in vertebrate developmental patterning and morphogenesis. Our study uncovers both maternal and zygotic contributions of  brd2 , the analysis of which may provide insight into the earliest events in vertebrate development, and the etiology of some forms of epilepsy, for which zebrafish is an important model. Knockdowns of  brd2  paralogs in zebrafish may now test proposed function and interaction with homeotic loci in vertebrates, and help reveal the extent to which functional novelty or partitioning has occurred after gene duplication.

bmc developmental biology

Zebrafish brd2a and brd2bare paralogous members of the bromodomain-ET (BET) family of transcriptional coregulators that show structural and expression divergence