brlA ("bristle") is a C2H2 zinc-finger transcription factor that acts as the master regulator of asexual sporulation (conidiation) in Aspergillus nidulans. It is necessary and sufficient to direct the developmental switch from indeterminate apical hyphal growth to the budding growth pattern of the conidiophore. BrlA is the top-tier regulator of the brlA -> abaA -> wetA central regulatory pathway: its expression, induced by the upstream FluG/Flb developmental-competence machinery, activates abaA and wetA and drives conidiophore morphogenesis, cessation of vegetative growth, and conidium (spore) formation. BrlA binds sequence-specific DNA response elements (BREs) and functions in the nucleus. The locus comprises two overlapping, individually required transcription units (brlAalpha and brlAbeta). Beyond its core role, brlA activity also influences secondary metabolism (sterigmatocystin biosynthesis) and asexual-sporulation-associated autolysis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: Core molecular function. BrlA is an RNA Pol II transcription factor. Reason: Consistent with the direct experimental IDA annotation to GO:0003700 (PMID:8417986), which showed BrlA activates transcription from specific DNA response elements. The IBA phylogenetic call agrees with the experimental evidence. |
| GO:0000987 cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: Accept. BrlA binds sequence-specific cis-regulatory elements (BREs). Reason: BrlA response elements (BREs) were identified as specific upstream DNA sites bound by BrlA, supporting sequence-specific cis-regulatory DNA binding. Supporting Evidence: PMID:8417986 Multiple copies of a synthetic oligonucleotide with the consensus sequence identified among the BREs mediated brlA-dependent transcriptional activation in yeast |
| GO:0042594 response to starvation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Keep as non-core. Nutrient starvation is a physiological cue that induces brlA and hence conidiation; this is a regulatory input rather than a core function. Reason: The IBA is phylogenetically propagated, but it is concordant with direct A. nidulans evidence (PMID:7894714, IEP) that starvation modulates brlA expression. Nutrient limitation is a well-established trigger of conidiation, so the link is real but non-core; kept consistent with the IEP annotation to the same term rather than marked as over-annotated. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Accept. BrlA is a transcription factor acting in the nucleus. Reason: Nuclear localization is expected and consistent for a DNA-binding transcriptional regulator; corroborated by the UniProt subcellular-location IEA annotation. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Accept. Nuclear location from UniProt subcellular-location mapping; consistent with TF role. Reason: Redundant with the IBA nucleus annotation but independently supported by the UniProtKB-SubCell mapping. Retain as a location annotation. |
| GO:0006357 regulation of transcription by RNA polymerase II | IEA GO_REF:0000117 | ACCEPT | Summary: Accept. BrlA regulates transcription of developmental target genes. Reason: Consistent with the IDA annotation (PMID:8417986) that BrlA activates transcription from BRE-containing promoters; this ARBA electronic annotation agrees. |
| GO:0010913 regulation of sterigmatocystin biosynthetic process | IMP PMID:9339347 Dominant mutations affecting both sporulation and sterigmato... | KEEP AS NON CORE | Summary: Keep as non-core. Real secondary-metabolism regulatory role, distinct from the core conidiation master-switch function. Reason: Dominant brlA-related mutations affect both sporulation and sterigmatocystin (ST) biosynthesis, linking brlA to ST regulation. This is a genuine but pleiotropic, non-core role. Supporting Evidence: PMID:9339347 we have found that 19 of these mutants are not only developmentally altered but also fail to produce the toxic, carcinogenic, secondary metabolite sterigmatocystin PMID:9339347 Another of the mutants results from a dominant interfering mutation in brlA. |
| GO:0045461 sterigmatocystin biosynthetic process | IMP PMID:9339347 Dominant mutations affecting both sporulation and sterigmato... | MARK AS OVER ANNOTATED | Summary: Over-annotated. BrlA is a regulator, not a component of the sterigmatocystin biosynthetic pathway. Reason: BrlA influences ST biosynthesis only as an upstream regulator; the regulatory relationship is already captured precisely by GO:0010913 (regulation of sterigmatocystin biosynthetic process). Annotating BrlA to the biosynthetic process itself overstates its role. Proposed replacements: regulation of sterigmatocystin biosynthetic process |
| GO:0048315 conidium formation | IMP PMID:2823119 Isolation and physical characterization of three essential c... | ACCEPT | Summary: Core function. BrlA is an essential conidiation gene required for conidium formation. Reason: brlA is one of the essential conidiation genes; loss blocks conidiophore/conidium formation. This is a core biological process for the gene. Supporting Evidence: PMID:3293800 The brlA gene of A. nidulans mediates the developmental switch from the indeterminate, apical growth pattern of vegetative cells to the budding growth pattern of conidiophores |
| GO:0048315 conidium formation | IMP PMID:3293800 brlA is necessary and sufficient to direct conidiophore deve... | ACCEPT | Summary: Core function (duplicate reference). BrlA is necessary and sufficient for conidiophore development. Reason: Forced brlA expression is sufficient to direct conidiophore development, and brlA loss abolishes it. Supporting Evidence: PMID:3293800 The brlA gene of A. nidulans mediates the developmental switch from the indeterminate, apical growth pattern of vegetative cells to the budding growth pattern of conidiophores. PMID:3293800 Misscheduled expression of brlA in vegetative cells results in transcriptional activation of developmentally regulated genes, cessation of unidirectional hyphal growth, initiation of cellular transformations resembling those that occur during normal conidiophore development, and production of viable conidiospores. |
| GO:0048315 conidium formation | IMP PMID:8508770 Translational repression of brlA expression prevents prematu... | ACCEPT | Summary: Core function (duplicate). Tight (translational) control of brlA gates conidium formation. Reason: brlA activity is required for conidium formation; its expression is translationally repressed to prevent premature development. |
| GO:1900376 regulation of secondary metabolite biosynthetic process | IMP PMID:9339347 Dominant mutations affecting both sporulation and sterigmato... | KEEP AS NON CORE | Summary: Keep as non-core. Parent-level secondary-metabolite regulatory role (via ST). Reason: Broader parent of the ST-regulation annotation (GO:0010913); reflects a real but non-core, pleiotropic role of brlA in coupling development to secondary metabolism. |
| GO:0000905 sporocarp development involved in asexual reproduction | IMP PMID:17030990 Upstream and downstream regulation of asexual development in... | ACCEPT | Summary: Core function. brlA drives development of the conidiophore (asexual sporocarp). Reason: brlA is required for conidiophore (asexual reproductive structure) development, the structural axis of conidiation. This complements the conidium-formation (spore-cell axis) annotations. Supporting Evidence: PMID:17030990 Deletion of Af brlA completely eliminated conidiation in all conditions tested, indicating that the activation of Af brlA expression early in conidiophore development also represents a foremost and essential control point for initiating the conidiation pathway |
| GO:0006357 regulation of transcription by RNA polymerase II | IMP PMID:2655931 Interactions of three sequentially expressed genes control t... | ACCEPT | Summary: Accept. BrlA activates downstream developmental genes (abaA, wetA). Reason: brlA sits atop a dependent transcriptional pathway; its expression activates abaA and wetA, evidencing regulation of RNA Pol II transcription. Supporting Evidence: PMID:2655931 Expression of brlA in vegetative cells leads to activation of abaA and wetA, cessation of vegetative growth, cellular vacuolization, and spore formation |
| GO:0042594 response to starvation | IEP PMID:7894714 Starvation stress modulates the expression of the Aspergillu... | KEEP AS NON CORE | Summary: Keep as non-core. brlA expression responds to starvation; a regulatory input, not a core function. Reason: The IEP evidence reflects starvation-modulated brlA expression (nutrient limitation as a developmental cue), not a role for BrlA in executing the starvation response. Retain as non-core rather than removing, since the expression response is real. |
| GO:0075307 positive regulation of conidium formation | IMP PMID:8508770 Translational repression of brlA expression prevents prematu... | ACCEPT | Summary: Core function. BrlA positively regulates conidium formation. Reason: As the master activator of conidiation, brlA is a positive regulator of conidium formation; this regulation term precisely captures its role. |
| GO:0000905 sporocarp development involved in asexual reproduction | IMP PMID:8508769 The Aspergillus nidulans brlA regulatory locus consists of o... | ACCEPT | Summary: Core function (duplicate). Both brlA transcription units are required for conidiophore development. Reason: The brlA locus comprises overlapping alpha/beta transcription units individually required for conidiophore (asexual sporocarp) development. Supporting Evidence: PMID:8508769 the brlA locus consists of overlapping transcription units, designated alpha and beta |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:8417986 Identification of Aspergillus brlA response elements (BREs) ... | ACCEPT | Summary: Core molecular function (direct experimental). BrlA is a sequence-specific DNA-binding transcriptional activator. Reason: Expressed in yeast, BrlA activated transcription from Aspergillus BRE sequences placed upstream of a reporter, directly demonstrating DNA-binding transcription factor activity. Supporting Evidence: PMID:8417986 The results show that a primary activity of brlA is transcriptional activation |
| GO:0006357 regulation of transcription by RNA polymerase II | IDA PMID:8417986 Identification of Aspergillus brlA response elements (BREs) ... | ACCEPT | Summary: Accept (direct). BrlA regulates transcription via BRE elements. Reason: Direct demonstration of BRE-dependent transcriptional activation supports regulation of RNA Pol II transcription. |
| GO:0001896 autolysis | IMP PMID:19486415 Asexual sporulation signalling regulates autolysis of Asperg... | KEEP AS NON CORE | Summary: Keep as non-core. Downstream effect of asexual-sporulation signalling on autolysis via chitinase ChiB. Reason: Asexual sporulation signalling (including brlA) modulates autolysis through the chitinase ChiB. This is a downstream, pleiotropic consequence, not a core function. |
| GO:0006357 regulation of transcription by RNA polymerase II | IMP PMID:2823119 Isolation and physical characterization of three essential c... | ACCEPT | Summary: Accept (duplicate). Consistent with brlA's transcriptional-regulator role. Reason: Redundant with other regulation-of-transcription annotations; retained as supporting evidence from an essential-conidiation-gene study. |
| GO:0075307 positive regulation of conidium formation | IEP PMID:2823119 Isolation and physical characterization of three essential c... | ACCEPT | Summary: Core function (duplicate). brlA expression correlates with and drives conidiation. Reason: Expression-pattern evidence consistent with brlA as a positive regulator of conidium formation. |
| GO:0075307 positive regulation of conidium formation | IMP PMID:2823119 Isolation and physical characterization of three essential c... | ACCEPT | Summary: Core function (duplicate). Loss-of-function confirms positive regulation of conidiation. Reason: brlA mutants fail to conidiate, confirming a positive-regulatory role in conidium formation. |
| GO:0006357 regulation of transcription by RNA polymerase II | IMP PMID:3293800 brlA is necessary and sufficient to direct conidiophore deve... | ACCEPT | Summary: Accept (duplicate). Master-switch TF regulating developmental transcription. Reason: Consistent with brlA's role as a transcriptional master regulator of conidiophore development. |
| GO:0075307 positive regulation of conidium formation | IMP PMID:3293800 brlA is necessary and sufficient to direct conidiophore deve... | ACCEPT | Summary: Core function (duplicate). brlA is necessary and sufficient for conidiation. Reason: Necessity-and-sufficiency data establish brlA as a positive regulator of conidium formation. |
| GO:0075307 positive regulation of conidium formation | IMP PMID:5366214 A mutational analysis of conidial development in Aspergillus... | ACCEPT | Summary: Core function (duplicate). Classic mutational analysis of conidial development. Reason: Mutational analysis of conidiation supports brlA as a positive regulator of conidium formation. |
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