The DNA-binding network of Mycobacterium tuberculosi s

Abstract

Mycobacterium tuberculosis (MTB) infects 30% of all humans and kills someone every 20 – 30 seconds. Here we report genome-wide binding for ~80% of all predicted MTB transcription factors (TFs), and assayed global expression following induction of each TF. The MTB DNA binding network consists of ~16,000 binding events from 154 TFs. We identify >50 TF-DNA consensus motifs and >1,150 promoter binding events directly associated with proximal gene regulation. An additional ~4,200 binding events are in promoter windows and represent strong candidates for direct transcriptional regulation under appropriate environmental conditions. However, we also identify >10,000 “dormant” DNA binding events that cannot be linked directly with proximal transcriptional control, suggesting that widespread DNA binding may be a common feature that should be considered when developing global models of coordinated gene expression.

Structural Basis for the Regulation of the MmpL Transporters of Mycobacterium tuberculosis

“…For each protein we were able to identify a putative inverted repeat sequence located in one or more of the M. tuberculosis H37Rv genes encoding MmpL transporter proteins. These DNA sequences are in good agreement with both the consensus binding sequences and protein-DNA interactions determined by others (21). We found that the Rv3249c protein might act as a regulator for mmpS1/L1, mmpL11, and rv1067c and Rv1816 for mmpL13b and rv1094.…”

N -methylation of a bactericidal compound as a resistance mechanism in Mycobacterium tuberculosis

“…S4) (24). Our observation that Rv2887 regulates expression of Rv0560c is supported by a recent genome-wide analysis of regulatory interactions in Mtb using ChIP-Seq-and RNA-Seq-based assays (25). Introduction of the R81Q mutation into Rv2887 abolished its ability to bind 560c-prom DNA ( Fig.…”

Construction of an overexpression library for Mycobacterium tuberculosis

“…This set was augmented with Gateway Entry clones received from the Pathogen Functional Genomics Resource Center (J. Craig Venter Institute); for these genes, expression vectors were generated by Gateway cloning into pDNTF and pDTCF expression vectors [28]. Plasmids were electroporated into M. tuberculosis H37Rv [29].…”