Disease relevance of br

• Here we use a recombinant Sindbis virus as a tool to silence BR-C expression in the silkmoth Bombyx mori [1].
• Surprisingly, BRC and DFD proteins are expressed in distinct, nonoverlapping subsets of neuronal nuclei of the subesophageal ganglion even though both are required for its migration into the head capsule [2].
• Rearrangements and point mutations at the ecs locus that result in female sterility had no effect on synthesis of the chorion protein s70 [3].
• It may therefore be suggested that the chorion protein gene is not functionally associated with the ecs locus and that sterility is caused not by disruptions of the chorion protein gene but by lesions in the ecs gene itself [3].

High impact information on br

• The gene (LAZ3) encodes a 79 kDa protein containing six zinc-finger motifs and sharing amino-terminal homology with several transcription factors including the Drosophila tramtrack and Broad-complex genes, both of which are developmental transcription regulators [4].
• The mutation l(1)npr-1 is located at cytological location 2B5 on the X chromosome in Drosophila melanogaster [5].
• Thus the normal product of the l(1)npr-1 gene is required for regression of the 68C puff, and the l(1)npr-1 gene product allows expression of the Sgs-3 gene by interacting, either directly or indirectly, with DNA sequences near this glue protein gene [5].
• From the pattern of X-gal staining observed, lacZ expression likely reflects the regulatory influence of BRC enhancers on the convertant transposon [6].
• Finally, we show that the dronc promoter has BR-C interaction sites, and that it can be transactivated by a specific isoform of BR-C [7].

Biological context of br

• The broad (br) gene, encoding a family of C2H2 type zinc-finger DNA-binding proteins, has been shown to act as a crucial member of the 20-hydroxyecdysone (20E) regulatory hierarchy in the fruitfly, Drosophila melanogaster and the moth, Manduca sexta [8].
• Overall, our study implicated br in the regulation of mosquito vitellogenesis [8].
• The Drosophila Broad-Complex plays a key role in controlling ecdysone-regulated gene expression at the onset of metamorphosis [9].
• The 2B5 early puff locus corresponds to the Broad-Complex BR-C) and encodes a family of transcription factors whose members are induced by the molting hormone ecdysone [10].
• Five binding sites have been identified within the intron by DNAase I footprinting and a core consensus sequence has been derived which shares some identity with the consensus binding site of the Z2 protein to the Sgs-4 regulatory region [10].

Anatomical context of br

• Our demonstration that Ddc is a target of BR-C in the epidermis is the first direct evidence of a role for this early gene in a tissue other than the salivary glands [10].
• These BR isoforms were activated by 20E in fat bodies cultured in vitro and behaved as early genes, with a self-repressive autoregulatory loop that can be blocked by the protein inhibitor, cyclohexamide [8].
• Using RNA interference in an ecdysone-responsive Drosophila cell line, we show that DRONC is essential for ecdysone-mediated cell death, and that dronc upregulation in these cells is controlled by BR-C [7].
• In this study, we examine the temporal expression of transcripts encoding each BR-C zinc-finger isoform-including the newly discovered fourth zinc-finger domain-during the metamorphosis of imaginal discs which form the integumental structures of the adult head and thorax [11].
• We show that Notch signaling establishes the boundary between two types of post-mitotic epithelial cells, the Rhomboid- and the Broad-positive cells [12].

Associations of br with chemical compounds

• However, JH III repressed 20E activation of br in 3-to 5-day-old females, indicating a switch in hormonal commitment [8].
• In vitro experiments with cultured wing discs showed that BRC-Z1 expression and early metamorphic development are rendered steroid-independent in the usp mutant clones [13].
• Interestingly, methoprene specifically disrupts those metamorphic events dependent on the combined action of all BRC isoforms, while sparing those that require specific isoform subsets [14].
• This transition is prevented in Drosophila larvae mutated in the ecdysone-dependent 2B5 locus, in which Sgs3 is inactive and GEBF-I, a Glue Enhancer Binding Factor, is missing [15].
• Puff 2B5 reaches its normal size but does not regress after 6 h incubation with 20-OH ecdysone, as it does in normal stocks [16].

Physical interactions of br

• Both the transcript and a protein carrying this domain are present in the epidermis and a BR-C recombinant protein carrying the Z2 finger binds to the first intron of the Ddc gene [10].
• DNase I foot printing has identified four binding sites of the predominant Z2 isoform within a distal regulatory element that is required for maximal Ddc activity [17].

Regulatory relationships of br

• This gene encodes the BR-C Z1 transcription factor and its expression is directly regulated by ecdysone through the ecdysone receptor (EcR/Usp) [18].
• Finally, in the presence of JH, E75A can repress ecdysone activation of early genes including Broad-Complex [19].
• Ecdysone-induced expression of the caspase DRONC during hormone-dependent programmed cell death in Drosophila is regulated by Broad-Complex [7].
• We also show that drice expression is specifically controlled by the ecdysone-regulated transcription factor BR-C [20].
• We further show that Broad represses rhomboid cell autonomously [12].

Other interactions of br

• We have found that the BR-C is critical for the appropriate regulation of all three classes of ecdysone-inducible genes [9].
• Broad-complex, but not ecdysone receptor, is required for progression of the morphogenetic furrow in the Drosophila eye [21].
• Unlike E74 and E75 early genes, expression of br was activated in previtellogenic females, during a juvenile hormone (JH)-dependent period [8].
• We demonstrate that dronc gene expression is ablated or reduced in BR-C mutant flies [7].
• Mutations in the steroid-regulated genes BR-C and E93 differentially impact larval midgut cell death but do not affect the formation of adult midgut epithelia [22].

Analytical, diagnostic and therapeutic context of br

• We have used Northern blot analysis of RNA isolated from staged animals and cultured organs to study the transcription of three primary response regulatory genes, E75, BR-C and EcR [23].
• Epidermal cell-specific quantitation of dopa decarboxylase mRNA in Drosophila by competitive RT-PCR: an effect of Broad-Complex mutants [24].
• They were characterized by genetic complementation tests, molecular mapping and cytogenetic analysis of their effect on ecdysone-induced puffing and BR-C proteins binding to polytene chromosomes [25].
• Here we present our confocal analyses of BR-C immunofluorescence and appendage morphogenesis in Drosophila melanogaster (two appendages) and Drosophila virilis (four appendages) [26].
• Western blot analyses demonstrated that BR-C isoforms are induced at the onset of metamorphosis, each with unique kinetics of induction and repression [27].

References