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Abstract
Spx, a global transcriptional regulator in Bacillus subtilis, enables oxidative stress survival by activating genes for detoxification and thiol homeostasis. Unlike typical regulators, Spx interacts with the RNA polymerase α subunit (αCTD) before promoter recognition. Biochemical analyses revealed that only one Spx monomer forms an active RNAP complex. Residues G52, R91, and R92 in Spx, along with Y263 in αCTD, are critical for RNAP interaction and redox control. The conserved AGCA motif at −44 in Spx-responsive promoters mediates activation. Crosslinking suggests oxidized Spx remodels RNAP and repositions σ^A for proper core promoter engagement, defining a unique transcriptional activation mechanism.