brlA

UniProt ID: P10069
Organism: Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139)
Review Status: DRAFT
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Gene Description

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.

Existing Annotations Review

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.
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.

Core Functions

Master transcriptional regulator of conidiation: as a sequence-specific C2H2 zinc-finger DNA-binding transcription factor, BrlA activates the conidiophore developmental program (including abaA and wetA), switching hyphae from vegetative growth to asexual spore production.

Supporting Evidence:
  • PMID:8417986
    The results show that a primary activity of brlA is transcriptional activation
  • PMID:8417986
    Multiple copies of a synthetic oligonucleotide with the consensus sequence identified among the BREs mediated brlA-dependent transcriptional activation in yeast
  • 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.

References

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Notes

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