BR-C, Broad Complex, ecs, npr1, rbp
Gene model reviewed during 6.06
Stop-codon suppression (UGA) postulated (FBrf0243886); 1 of 2 cases for this gene.
Gene model reviewed during 6.32
Gene model reviewed during 5.44
Gene model reviewed during 5.39
Gene model reviewed during 5.42
Low-frequency RNA-Seq exon junction(s) not annotated.
Gene model reviewed during 5.45
Stop-codon suppression (UAA) postulated; FBrf0216884; 1 of 2 cases for this gene.
Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\br using the Feature Mapper tool.
Under conditions of nutritional shortage, initial expression detected later, at stage 6. Expression of different isoforms varies; BR-C Z2 and BR-C Z3 appear to mediate response to varying nutritional levels.
br transcript is localized to neuronal cell bodies in all parts of the adult brain. Expression levels in the adult optic lobe are lower than in the brain and subesophageal ganglion, with a region of particular intensity in a cluster of cells at the top of the cervical connective as it joins the subesophageal ganglion, and in cells surrounding the calyces of the mushroom bodies.
RNA blots were carried out on RNA extracted from staged larval and prepupal salivary glands. br transcripts are induced in apparent response to the late-larval and prepupal ecdysone pulses paralleling the puffing response at 2B5. This response is enhanced in response to ectopic ftz-f1 expression.
The major 4.5kb and minor 2, 7.4, 9.5, and 11.5kb br transcripts are present in ovaries and at low levels in embryonic and early larval stages. They rise dramatically in third instar through prepupal stages, consistent with being ecdysone-inducible.
Comment: Assay specific to Z3 isoform (br-RA). 72h-120h AEL
br protein is expressed in late third instar larval wing disc. A particular isoform of br protein (Br-Z1) was identified as the isoform that is strongly expressed in third instar larvae from 30 hours after the L2/L3 molt forward. Activation of br equires that larvae pass the critical weight, which normall occurs 8-12 hours after the L2/L3 molt. chinmo down-regulation correlates with br activation in the wing disc throughout L3.
Expression of br in pupal wing discs peaks at stage P3, and is undetectable by mid-stage-P6.
br protein is detected in late third instar and in pupal stages by western blot. A subset of isoforms are present in late pupal stages. Immunolocalizations shows br protein in fat body from late third instar larvae but not first or second instar larvae.
br protein is detected in the embryonic central nervous system and in a subset of neurons of the thoracic and abdominal neuromeres just after hatching. Specific labelling for the Z3 isoform (br-RA) shows expression in neuroblast clones in the thoracic neuromeres: at the start of late third instar (72h AEL) arrested embryonic-born secondary neurons strongly express Z3 isoform in the oldest neurons of the cluster (basal) whereas expression is absent from the younger neurons (apical). Weak expression of Z3 isoform in larval-born secondary neurons is observed in the oldest neurons of the cluster at 72h AEL, becoming stronger as late third instar progresses, and disappears by pupariation. At this stage, Z3 isoform is observed in the younger neurons of cluster, except for those nearest to the neuroblast. In late larval and pupal stages, Z3 isoform is detected in the optic lobe and in four neuron clusters in the mushroom bodies. Specific labelling for the Z1 isoforms (br-RE,RG,RM,RN,RO) or Z4 isoforms (br-RB,RC,RH,RI,RP,RQ) is observed in neurons and glia in the central nervous system in pupal stages. The neurons labelled by Z3 isoform antibody correspond to the neurons that are labelled by the antibody for br protein; the subset of glia and neurons marked by Z1 or Z4 isoforms correspond to smaller subsets of the br positive cells.
An antibody directed to the core domain shared by all of the protein isoforms labeled over 300 distinct areas on larval and prepupal salivary glands. Labeling was observed in large and small puff regions as well as interbands. Pericentric heterochromatic labeling was observed only in one region - 20D and 20E of the X chromosome. This staining correlates with that observed using an antibody specific for the Z1 isoform which has been reported to be the predominate br isoform in larval salivary glands. In contrast, Z2 and Z3 specific antibodies did not label salivary gland polytene chromosomes.
Expression of br protein in larval prothoracic gland is isoform-specific. The Z2 and Z3 isoforms are detectable 17 hours after ecdysis into the third instar (89 hr AEL), and continue to be expressed through the white prepupa stage. The Z4 isoform is intensely expressed in wandering third instar larvae and white prepupae; and the Z1 isoform initiates intense expression later in the third instar.
At wandering third instar larval stage, br protein is widely expressed in the central nervous system. Staining localized to the nuclei of central nervous system, with prominent labeling in the optic lobes, brain, subesophageal ganglion, and thoracic segments of the ventral nerve cord. Expression is also observed in cells at the midline of the ventral nerve cord. Staining is absent in the neuropil.
GBrowse - Visual display of RNA-Seq signalsView Dmel\br in GBrowse 2
Recombinational mapping experiments show that the 'rbp', 'l(1)2Bc' and 'broad' class alleles are separable by recombination.
Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete
Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.
For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.
Source for merge of: br CG11491
Source for merge of: br CG11514
Source for merge of: br l(1)G0318 l(1)G0401 l(1)G0018 l(1)G0042 l(1)G0284a
Source for merge of: br CG11511
Source for merge of: br CG11509
Annotation CG11491 merged with CG11509 in release 6.06 of the genome annotation; CG11509 corresponds to a portion of the 3' UTR of an alternative transcript isoform of br.
Annotations CG11491, CG11514 and CG11511 merged as CG11491 in release 3 of the genome annotation.
Russian investigators originally defined four mutually complementing, lethally mutable loci, which function in ecdysone-dependent induction of metamorphosis: br, broad, rbp, reduced bristles on palpus, l(1)2Bc, and l(1)2Bd. Based on amorphic mutations, defined on the basis of having equivalent phenotypes in homozygous and hemizygous females, Kiss et al. (FBrf0048202) define two complementation groups: br, comprising br, rbp and l(1)2Bd (Belyaeva et al., FBrf0045819), and l(1)2Bc; npr alleles are non-complementing.
Annotation (CG11509) restored in release 5.33 of the genome annotation.
Annotation (CG11509) eliminated in release 5.2 of the genome annotation.
The ecdysone pathway is required for proliferation and differentiation of hematopoitic precurssors of lamellocytes and crystal cells.
br isoforms regulate morphogenetic furrow progression and photoreceptor specification in the developing eye.
rbp+ function is required in the dorsal epidermal muscle attachment site for the correct attachment of the indirect flight muscles.
The target genes of the BR-C (br) in oogenesis include a protein essential for endoreplication and chorion gene amplification.
br encodes a family of zinc-finger DNA binding proteins generated by alternative splicing, which produces four classes of proteins; Z1, Z2, Z3 and Z4. The Z1 isoform provides full rbp+ function. Z2 provides br+ function (Z2 is the only protein isoform to provide br+ function), and partial 2Bc+ function. Z3 provides full 2Bc+ function. Z4 provides partial rbp+ function.
br is expressed in a bilaterally symmetrical pattern in the lateral-dorsal-anterior follicle cells during late oogenesis.
Wild-type rbp function is required for the correct and stable attachment of the thoracic muscles to the body wall, fasciculation and maintenance of these thoracic muscles. The primary effect of rbp mutations is to disrupt muscle attachment, causing muscles to choose incorrect sites or to make weak attachments that ultimately fail.
The ecdysone response of individual br zinc finger RNA isoforms is examined in cultured imaginal discs. Studies reveal a complex temporal pattern of RNA expression.
The br complex (BR-C) early gene encoded by the Z1 isoform (rbp) directly activates late gene transcription (genes from the 71E salivary glands late puff) by interacting with late gene cis-acting regulatory elements and this interaction is responsible for the temporal linkage of early and late ecdysone-induced gene expression.
A transgene containing the Z1 isoform can rescue a mutant 'rbp' phenotype. A transgene containing the Z2 isoform can rescue a mutant br phenotype and can partially rescue the mutant lethality of 'l(1)2Bc'. A transgene containing the Z3 isoform can rescue the mutant lethality of 'l(1)2Bc'.
P-element rescue constructs suggest that the Z1 isoform of the BRC corresponds to 'rbp' function, and the Z2 isoform to 'br' function, but that there is no simple correlation between any one BRC protein and 'l(1)2Bc' function.
Analysis of morphological and molecular phenotypes of double mutants between alleles of br and Eip74EF reveals that br and Eip74EF share functions in puparium formation, pupation and early gene induction. The br and Eip74EF transcription factors may directly interact to regulate the expression of salivary gland glue and late genes.
ImpE1 and Dfd have been examined for their positions relative to the Broad complex genes in the hormone-regulated pathway of CNS metamorphosis. Activity of any individual Broad complex subfunction is not required for ImpE1 induction.
Mapping of DNase hypersensitive sites (DHS) in mutants reveals changes in chromatin structure associated with sites that presumably contain target sequence for the BR-C gene products.
Differential expression of Broad complex transcription factors may forecast tissue-specific developmental fates during metamorphosis.
Both 'rbp' and 'l(1)2Bc' are required for glue gene induction in mid-third instar larvae. The intermolt secondary-response genes and the late secondary-response genes are absolutely dependent on br for the induction. In addition the 'l(1)2Bc' function is required for glue gene repression in prepupae and the complete ecdysone induction of early mRNAs from Eip74EF, Eip75B and the broad complex itself.
Mosaic experiments reveal a somatic but not germ line requirement for npr function.
The temporal pattern of br transcription during the third larval instar stage has been analysed.
When the 2B region is subjected to position effect the br locus in inactivated.
'rbp' function is necessary for intermoult and late transcription in salivary glands. Transcription of genes in the ecdysone-induced puffing cascade is dependent on 'rbp' function.
The npr wild type gene product, which is necessary for the activation of intermoult glue genes, is necessary for the inactivation of the pre-moult genes.
br has been located within a puff on the telomeric chromosome of D.funebris, D.virilis, D.hydei, D.repleta, D.mercatorum and D.paranaensis, within a puff on the distal part of the X chromosome of D.kanekoi and within a puff on the proximal portion of the X chromosome of D.pseudoobscura.pseudoobscura.
Ovaries from fertile females transplanted into br mutant females succeeded in connecting to recipient oviducts suggesting that female sterile mutations at the br locus are somatic line specific: abnormal morphogenesis of their genital disc is due to loss of normal sensitivity to ecdysterone.
The steroid hormone 20-hydroxyecdysone can regulate RNA levels of a single gene both positively and negatively depending on hormone concentration. br can modify the direction of the gene's response to a hormone signal.
Mutations at br reduce the transcription rate or stability of the small heat shock protein mRNAs.
'l(1)2Bc' is involved in imaginal disc fusion. br is involved in imaginal disc evagination.
'br' and 'l(1)2Bc' alleles are fully complementing.
'l(1)2Bc' function is involved in appendage elongation.
The br complementation group contains both amorphic and hypomorphic mutant alleles; amorphic alleles cause early prepupal developmental arrest; hypomorphic alleles cause late pupal or pharate adult developmental arrest or are viable. Null alleles display normal larval development but prevent elongation and eversion of discs giving rise to appendages in the pupal stage. Wings of the viable allele, br1, somewhat broader than normal; about 80% of normal length, with round full tip; crossveins closer together. Shape difference visible in middle prepupal stage immediately after eversion (FBrf0004792; FBrf0005070). A haplo-insufficient locus in that heterozygosity for a deficiency including the br locus leads to a slight br phenotype (FBrf0034402); furthermore, the deficiency in combination with br1 or br3 leads to drastic reduction in viability, especially at 18oC, and an extreme phenotype among survivors, including reduced palpi characteristic of 'rbp' alleles, short rounded wings with interrupted veins and malformed third legs, i.e., shortened and thickened femora and tibiae as well as misshapen basitarsi. The malformed-leg syndrome is enhanced by heterozygosity for Sb alleles (FBrf0048216). br16/+ and Df(1)S39/+ display slight dominance of br effects in the presence of RpII215Ubl (FBrf0035975). Hemizygous 'npr' male larvae fail to pupariate, although they survive 10-15 days after their normal sibs have pupariated. Four-day-old larvae appear normal as do their imaginal discs; normal ecdysteroid levels achieved. Discs become abnormal beginning on the sixth day; peripodial membrane becomes enormously distended and highly distorted; partially evaginated structure becomes visible in the disc lumen; do not undergo detailed morphological changes characteristic or metamorphosis, either in situ or in transplants into normal larvae (FBrf0037303). Both salivary glands and fat bodies fail to undergo histolysis in situ or in vitro. 'npr' mutant flies able to produce ecdysone, but tissues are unable to respond normally. In gynandromorphs, the female tissue forms a puparium, whereas 'npr' male tissue remains larval; no adults survive (FBrf0032169; FBrf0029263). Implantation of wild-type ring glands into 'npr' larvae does not rescue pupariation; however implanted wild-type or 'npr' ring glands are able to rescue brnpr-3 larvae (FBrf0034101). 'npr' alleles fail to show regression of the intermolt 68C glue puff (FBrf0035971; FBrf0040472) or induction of ecdysone induced 'early' puffs in larval salivary gland polytene chromosomes. 'rbp' alleles are late pupal lethal; most animals reach the pharate adult stage. Viable 'rbp' adults have a reduced number of bristles on the maxillary palpus, and may show other bristle and wing defects.
br encodes a family of Zinc-finger proteins that possess both common and unique exons. The gene is expressed as an 'early' ecdysone puff in 2B1--2B5 in salivary gland polytene chromosomes. A consequence of the molecular organization of the br gene is a complex pattern of complementation between mutant alleles.