Dual DNA binding and coactivator functions of Aspergillus nidulans TamA, a Zn(II)2Cys6 transcription factor

Abstract

SummaryTranscription factors containing DNA binding domains generally regulate transcription by direct interaction with DNA. For most transcription factors, including the fungal Zn(II)2Cys6 zinc binuclear cluster transcription factors, the DNA binding motif is essential for function. However, Aspergillus nidulans TamA and the related Saccharomyces cerevisiae Dal81p protein contain Zn(II)2Cys6 motifs shown to be dispensable for function. TamA acts at several promoters as a coactivator of the global nitrogen GATA transcription factor AreA. We now show that TamA is the major transcriptional activator of gdhA, encoding the key nitrogen metabolism enzyme NADP-glutamate dehydrogenase. Moreover, activation of gdhA by TamA occurs primarily by a mechanism requiring the TamA DNA binding motif. We show that the TamA DNA binding motif is required for DNA binding of FLAGepitope-tagged TamA to the gdhA promoter. We identify a conserved promoter element required for TamA activation, and show that TamA and AreA are reciprocally required for full binding at the gdhA promoter under conditions where AreA is inactive at most promoters but active at gdhA. Therefore TamA has dual functions as a DNA-binding transcription factor and a non-DNA-binding coactivator. Dual DNA-binding and coactivator functions provide an additional level of combinatorial control to mediate gene-specific expression.

The fungal‐specific transcription factor Vdpf influences conidia production, melanized microsclerotia formation and pathogenicity in Verticillium dahliae

“…In A. flavus , the Zn(II) 2 Cys 6 zinc cluster‐encoding gene family is involved in asexual conidiation, sexual homothallic development and secondary metabolites (Chang and Ehrlich, ). In A. nidulans , TamA interacts with LeuB and regulates leucine biosynthesis, NADP‐glutamate dehydrogenase activity and nitrogen metabolism through the regulation of the gdhA gene encoding NADP‐glutamate dehydrogenase (Downes et al ., ). In A. oryzae , ManR, a novel Zn(II) 2 Cys 6 transcriptional activator, controls the β‐mannan utilization system (Ogawa et al ., ).…”

Nitrogen regulation of fungal secondary metabolism in fungi

“…In A. nidulans , full activation of some AreA-dependent genes, e.g., gdhA , requires also the function of a Zn(II)2Cys6 zinc binuclear cluster transcription factor, TamA, a homolog of the S. cerevisiae Dal81p protein ( Davis et al, 1996 ). Recently it has been shown, that TamA has dual functions as a DNA-binding transcription factor and a non-DNA-binding co-activator of AreA which interacts with the C-terminal residues of AreA ( Davis et al, 1996 ; Downes et al, 2013 , 2014 ). At present the role of TamA has not been characterized in any other fungus.…”

Tpc1 is an important Zn(II)2Cys6 transcriptional regulator required for polarized growth and virulence in the rice blast fungus

“…Most Zn(II) 2 Cys 6 proteins have been studied in Saccharomyces cerevisiae and Aspergillus species[ 13 , 15 , 16 ]. Typically, the Zn(II) 2 Cys 6 proteins are pathway-specific activators under the control of major regulators[ 15 , 16 , 17 , 18 ]. The regulator of galactose catabolism in yeast, Gal4p[ 19 ], and the regulators of acetate assimilation FacB[ 20 ] and the aflatoxin cluster AflR[ 21 ] in A .…”