Genomic mapping of cAMP receptor protein (CRP super(Mt)) in Mycobacterium tuberculosis: relation to transcriptional start sites and the role of CRP super(Mt) as a transcription factor

Chromatin immunoprecipitation identified 191 binding sites of Mycobacterium tuberculosis cAMP receptor protein (CRP super(Mt)) at endogenous expression levels using a specific alpha -CRP super(Mt) antibody. Under these native conditions an equal distribution between intragenic and intergenic locations was observed. CRP super(Mt) binding overlapped a palindromic consensus sequence. Analysis by RNA sequencing revealed widespread changes in transcriptional profile in a mutant strain lacking CRP super(Mt) during exponential growth, and in response to nutrient starvation. Differential expression of genes with a CRP super(Mt)-binding site represented only a minor portion of this transcriptional reprogramming with 19% of those representing transcriptional regulators potentially controlled by CRP super(Mt). The subset of genes that are differentially expressed in the deletion mutant under both culture conditions conformed to a pattern resembling canonical CRP regulation in Escherichia coli, with binding close to the transcriptional start site associated with repression and upstream binding with activation. CRP super(Mt) can function as a classical transcription factor in M. tuberculosis, though this occurs at only a subset of CRP super(Mt)-binding sites.