Pathways for transcriptional activation of a glutathione-dependent formaldehyde dehydrogenase gene.
The widespread occurrence of glutathione-dependent formaldehyde dehydrogenases (GSH-FDH) suggests that this enzyme serves a conserved function in preventing the cytogenetic and potentially lethal interaction of formaldehyde with nucleic acids, proteins and other cell constituents. Despite this potential role of GSH-FDH, little is known about how its expression is regulated. Here, we identify metabolic and genetic signals that activate transcription of a GSH-FDH gene (adhI) in the bacterium Rhodobacter sphaeroides. Activity of the adhI promoter is increased by both exogenous formaldehyde and metabolic sources of this toxin. Elevated adhI promoter activity in DeltaGSH-FDH mutants implicates formaldehyde or the glutathione adduct that serves as a GSH-FDH substrate, S-hydroxymethylglutathione, as a transcriptional effector. From studying adhI expression in different host mutants, we find that the photosynthetic response regulator PrrA and the trans-acting spd-7 mutation increase function of this promoter. The behavior of a nested set of adhI::lacZ fusions indicates that activation by formaldehyde, PrrA and spd-7 requires only sequences 55 bp upstream of the start of transcription. A working model is presented to explain how GSH-FDH expression responds to formaldehyde and global signals generated from the reduced pyridine nucleotide produced by the activity of this enzyme.
Barber
R D
RD
Graduate Program in Cell and Molecular Biology, University of Wisconsin at Madison, Madison, WI 43706, USA.
Donohue
T J
TJ
D000445:Aldehyde Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D000483:Alleles; D019175:DNA Methylation; D005557:Formaldehyde / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial / Q000235:genetics*; D005978:Glutathione / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012242:Rhodobacter sphaeroides / Q000201:enzymology* / Q000235:genetics; D015533:Transcriptional Activation
D005557:Formaldehyde; C020145:formaldehyde dehydrogenase (glutathione); D000445:Aldehyde Oxidoreductases; D005978:Glutathione