title: Reprogramming of carbon metabolism by the transcriptional activators AcuK and AcuM in Aspergillus nidulans.
abstract: The ability of fungi to use carbon sources metabolized via the TCA cycle requires gluconeogenesis. In Aspergillus nidulans the AcuK and AcuM transcription factors regulate the expression of the gluconeogenic genes acuF, encoding phosphoenolpyruvate carboxykinase, and acuG, encoding fructose-1,6-bisphosphatase. Expressed proteins containing the AcuK/AcuM N-terminal DNA-binding domains bind together in vitro to motifs containing repeats of CGG separated by seven bases (CCGN7CCG) and the functionality of these sequences was verified in vivo by acuF-lacZ reporter studies. Chromatin immunoprecipitation analysis showed inter-dependent DNA binding of the proteins to the promoters of gluconeogenic genes in vivo independent of the carbon source. Deletion of the mdhC gene encoding a cytoplasmic/peroxisomal malate dehydrogenase showed that this activity is not essential for gluconeogenesis and indicated that induction of AcuK/AcuM regulated genes might result from malate accumulation. Deletion of the gene for the alternative oxidase did not affect growth on gluconeogenic carbon sources; however, expression was absolutely dependent on AcuK and AcuM. Orthologues of AcuK and AcuM, are present in a wide range of fungal taxa and the CCGN7CCG motif is present in the 5' of many genes involved in gluconeogenesis indicating a fundamental role for these transcription factors in reprogramming fungal carbon metabolism.
authors.affiliation: Department of Genetics, University of Melbourne, Melbourne, Vic. 3010, Australia.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Murray
authors.forename: Koon Ho
authors.initials: KH
authors.lastname: Wong
authors.forename: Meryl A
authors.initials: MA
authors.lastname: Davis
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hynes
mesh_terms: D001233:Aspergillus nidulans / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002244:Carbon / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D002952:Citric Acid Cycle; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D015966:Gene Expression Regulation, Fungal; D005943:Gluconeogenesis; D060847:Metabolic Engineering; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; D002244:Carbon; D004247:DNA