Redox-responsive transcriptional regulator that regulates a set of genes involved in protection against environmental stresses encountered during infection. The loss of the O(2) and NO-responsive 4Fe-4S cluster and subsequent redox modifications of Cys residue thiols (possibly by disulfide bond formation) may activate its role in gene regulation. The thiol-oxidized apo-form binds in a sequence non-specific manner to GC-rich DNA, probably in the minor groove. Represses transcription of a number of genes including itself. The reduced apo-form and holo-form do not bind DNA. The apo-form can act as protein disulfide reductase. Binds 1 [4Fe-4S] cluster per subunit. The cluster responds to both O(2) and NO. Following nitrosylation of the [4Fe-4S] cluster binds 1 [4Fe-8(NO)] cluster per subunit. Homodimer in the presence of reducing agents (PubMed:17302817); the oxidized apo-form makes dimers and trimers while the redeced apo-form does not (PubMed:22780904). Upon over expression in aerobically grown M.smegmatis, apo-WhiB4 forms trimers held together by disulfide bonds. The 4Fe-4S cluster is very sensitive to air, degrading from 4Fe-4S via 3Fe-3S to 2Fe-2S then cluster loss. Upon cluster removal intramolecular disulfide bonds are formed. Can be nitrosylated by NO, leading to the formation of a tetrakis-cysteinyl [Fe4-(NO)8] complex. Fully oxidized recombinant protein tagged at both termini. Fully reduced recombinant protein tagged at both termini. During aerobic growth in culture grows more slowly over the whole life cycle, a 2X reduced ratio of NAD(+)/NADH (reflects redox metabolism) and a 1.5X reduction in membrane potential. Has increased resistance to oxidative stress. Enhanced growth in uninduced and activated macrophages, as well as enhanced growth at reduced O(2) tension. However reduced survival in guinea pig spleen but not lungs following aerosol infection. A number of genes are induced, including whiB4, whiB6, genes involved in antioxidant systems, redox factor PQQ and several members of the PE-PPE family. Belongs to the WhiB family.