The etiological agent of tuberculosis, Mycobacterium tuberculosis, causes the deaths of two million people annually. Therefore, it is suggested that WhiB1 acts to oppose Cmr-mediated cAMP-independent activation of groEL2 expression in the presence of nitric oxide by promoter occlusion. The CRP-family transcription factor Cmr (Rv1675c) was shown to bind the groEL2 promoter and activate transcription in vitro in the presence or absence of cAMP. DNase I footprinting identified a WhiB1-binding region that overlapped the −35 element of the groEL2 promoter. Electrophoretic mobility shift assays with sub-fragments of the groEL2 promoter indicated that the complete Rv0439c-Rv0440 intergenic region was required for WhiB1 binding, suggesting that this region possessed more than one WhiB1-binding site. Apo-WhiB1 inhibited transcription from the groEL2 promoter in vitro and the transcript start was located ∼181 bases upstream of the groEL2 start codon. Here it is shown that apo-WhiB1 binds to groEL2 ( Rv0440) promoter DNA. Recently, WhiB1 was identified as a nitric oxide-responsive transcription factor. Nitric oxide produced by infected lung macrophages promotes expression of genes associated with dormancy, and impaired nitric oxide production can lead to reactivation of latent disease. A central feature of TB pathogenesis is the formation of Mycobacterium tuberculosis latent infections that can persist for decades.
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