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Gene Review

br  -  broad

Drosophila melanogaster

Synonyms: 2B5, 2Bc, A18, BR, BR-C, ...
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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


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


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


  1. Use of Sindbis virus-mediated RNA interference to demonstrate a conserved role of Broad-Complex in insect metamorphosis. Uhlirova, M., Foy, B.D., Beaty, B.J., Olson, K.E., Riddiford, L.M., Jindra, M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  2. Parallel molecular genetic pathways operate during CNS metamorphosis in Drosophila. Restifo, L.L., Hauglum, W. Mol. Cell. Neurosci. (1998) [Pubmed]
  3. Cytogenetical analysis of the 2B3-4-2B11 region of the X chromosome of Drosophila melanogaster. VII. Influence of the ecs locus on female fertility. Mazina, O.M., Belyaeva, E.S., Zhimulev, I.F. Mol. Gen. Genet. (1991) [Pubmed]
  4. LAZ3, a novel zinc-finger encoding gene, is disrupted by recurring chromosome 3q27 translocations in human lymphomas. Kerckaert, J.P., Deweindt, C., Tilly, H., Quief, S., Lecocq, G., Bastard, C. Nat. Genet. (1993) [Pubmed]
  5. A trans-acting regulatory product necessary for expression of the Drosophila melanogaster 68C glue gene cluster. Crowley, T.E., Mathers, P.H., Meyerowitz, E.M. Cell (1984) [Pubmed]
  6. Enhancer-trap targeting at the Broad-Complex locus of Drosophila melanogaster. Gonzy-Tréboul, G., Lepesant, J.A., Deutsch, J. Genes Dev. (1995) [Pubmed]
  7. Ecdysone-induced expression of the caspase DRONC during hormone-dependent programmed cell death in Drosophila is regulated by Broad-Complex. Cakouros, D., Daish, T., Martin, D., Baehrecke, E.H., Kumar, S. J. Cell Biol. (2002) [Pubmed]
  8. The early gene Broad is involved in the ecdysteroid hierarchy governing vitellogenesis of the mosquito Aedes aegypti. Chen, L., Zhu, J., Sun, G., Raikhel, A.S. J. Mol. Endocrinol. (2004) [Pubmed]
  9. The Drosophila Broad-Complex plays a key role in controlling ecdysone-regulated gene expression at the onset of metamorphosis. Karim, F.D., Guild, G.M., Thummel, C.S. Development (1993) [Pubmed]
  10. Hormonal induction of Dopa decarboxylase in the epidermis of Drosophila is mediated by the Broad-Complex. Hodgetts, R.B., Clark, W.C., O'Keefe, S.L., Schouls, M., Crossgrove, K., Guild, G.M., von Kalm, L. Development (1995) [Pubmed]
  11. A switch in broad-complex zinc-finger isoform expression is regulated posttranscriptionally during the metamorphosis of Drosophila imaginal discs. Bayer, C.A., Holley, B., Fristrom, J.W. Dev. Biol. (1996) [Pubmed]
  12. Border of Notch activity establishes a boundary between the two dorsal appendage tube cell types. Ward, E.J., Zhou, X., Riddiford, L.M., Berg, C.A., Ruohola-Baker, H. Dev. Biol. (2006) [Pubmed]
  13. The RXR ortholog USP suppresses early metamorphic processes in Drosophila in the absence of ecdysteroids. Schubiger, M., Truman, J.W. Development (2000) [Pubmed]
  14. A juvenile hormone agonist reveals distinct developmental pathways mediated by ecdysone-inducible broad complex transcription factors. Restifo, L.L., Wilson, T.G. Dev. Genet. (1998) [Pubmed]
  15. GEBF-I activates the Drosophila Sgs3 gene enhancer by altering a positioned nucleosomal core particle. Georgel, P., Dretzen, G., Jagla, K., Bellard, F., Dubrovsky, E., Calco, V., Bellard, M. J. Mol. Biol. (1993) [Pubmed]
  16. Cytogenetic analysis of the 2B3-4-2B11 region of the X chromosome of Drosophila melanogaster. II. Changes in 20-OH ecdysone puffing caused by genetic defects of puff 2B5. Belyaeva, E.S., Vlassova, I.E., Biyasheva, Z.M., Kakpakov, V.T., Richards, G., Zhimulev, I.F. Chromosoma (1981) [Pubmed]
  17. Control of Dopa decarboxylase gene expression by the Broad-Complex during metamorphosis in Drosophila. Chen, L., O'Keefe, S.L., Hodgetts, R.B. Mech. Dev. (2002) [Pubmed]
  18. Temporal regulation of Drosophila salivary gland degeneration by the Broad-Complex transcription factors. Kuchárová-Mahmood, S., Raska, I., Mechler, B.M., Farkas, R. J. Struct. Biol. (2002) [Pubmed]
  19. Hormonal regulation and functional role of Drosophila E75A orphan nuclear receptor in the juvenile hormone signaling pathway. Dubrovsky, E.B., Dubrovskaya, V.A., Berger, E.M. Dev. Biol. (2004) [Pubmed]
  20. Ecdysone-mediated up-regulation of the effector caspase DRICE is required for hormone-dependent apoptosis in Drosophila cells. Kilpatrick, Z.E., Cakouros, D., Kumar, S. J. Biol. Chem. (2005) [Pubmed]
  21. Broad-complex, but not ecdysone receptor, is required for progression of the morphogenetic furrow in the Drosophila eye. Brennan, C.A., Li, T.R., Bender, M., Hsiung, F., Moses, K. Development (2001) [Pubmed]
  22. Steroid regulation of midgut cell death during Drosophila development. Lee, C.Y., Cooksey, B.A., Baehrecke, E.H. Dev. Biol. (2002) [Pubmed]
  23. Temporal coordination of regulatory gene expression by the steroid hormone ecdysone. Karim, F.D., Thummel, C.S. EMBO J. (1992) [Pubmed]
  24. Epidermal cell-specific quantitation of dopa decarboxylase mRNA in Drosophila by competitive RT-PCR: an effect of Broad-Complex mutants. O'Keefe, S., Schouls, M., Hodgetts, R. Dev. Genet. (1995) [Pubmed]
  25. Isolation and characterization of novel mutations of the Broad-Complex, a key regulatory gene of ecdysone induction in Drosophila melanogaster. Gonzy, G., Pokholkova, G.V., Peronnet, F., Mugat, B., Demakova, O.V., Kotlikova, I.V., Lepesant, J.A., Zhimulev, I.F. Insect Biochem. Mol. Biol. (2002) [Pubmed]
  26. Temporal comparison of Broad-Complex expression during eggshell-appendage patterning and morphogenesis in two Drosophila species with different eggshell-appendage numbers. James, K.E., Berg, C.A. Gene Expr. Patterns (2003) [Pubmed]
  27. Differential expression of Broad-Complex transcription factors may forecast tissue-specific developmental fates during Drosophila metamorphosis. Emery, I.F., Bedian, V., Guild, G.M. Development (1994) [Pubmed]
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