Alternative Sigma Factors ________________________________________________

Jayanta Mukhopadhyay

Alternative sigma factors of Mycobacterium tuberculosis in global gene regulation

The M. tuberculosis genome encodes ~4000 proteins that include ~180 transcriptional regulators, 13 sigma factors (sig A - sig M), and 11 two component systems.

Some of the sigma factors of M. tuberculosis respond to environmental stress such as cold shock, heat shock, hypoxia, iron starvation, surface stress, and oxidative stress, while others respond to currently unknown environmental conditions.

 Results taken from quantitative reverse-transcription PCR/microarray technology, and chromatin immunoprecipitation assay, allowed the partial characterization of seven sigma factors and proposed consensus sequences of six sigma factors.

Comprehensive characterization of  sigma factor binding sites and targets, is still lacking.

 Hence we aim: 
  • To determine the binding specificity of each of 13 sigma factors using recombinant Mtb RNA polymerase and SELEX method.
  • To identify the promoters for each sigma factor by comparing its binding specificity sequence with intergenic regions of Mtb genome.
  • To identify the genes directly regulated by each sigma factor by microarray analysis of mRNA from in vitro transcription assays with Mtb RNA polymerase and genomic DNA.