TY - JOUR T1 - RsrR: a novel redox sensitive Rrf2 family transcription factor in <em>Streptomyces venezuelae</em> JF - bioRxiv DO - 10.1101/050989 SP - 050989 AU - John T. Munnoch AU - Ma Teresa Pellicer Martinez AU - Dimitri A. Svistunenko AU - Jason C. Crack AU - Nick E. Le Brun AU - Matthew I. Hutchings Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/04/29/050989.abstract N2 - Members of the Rrf2 superfamily of transcription factors are widespread in bacteria but their biological functions are largely unknown. The few that have been characterised in detail sense nitric oxide (NsrR), iron limitation (RirA), cysteine availability (CymR) and the iron sulphur (Fe-S) cluster status of the cell (IscR). Here we combine ChIP-seq, ChIP-exo and dRNA-seq with in vitro biochemistry to characterise a new member of the Rrf2 family in the model organism Streptomyces venezuelae. We show that Sven6563 has a redox active [2Fe-2S] cluster and that the switch from oxidized to reduced cluster switches off DNA binding activity. We have named the protein RsrR for Redox sensitive response Regulator. Binding site positions at target promoters combined with expression data suggest RsrR acts primarily as a repressor, like other Rrf2 proteins. ChIP shows that RsrR can bind to class 1 target promoters containing an 11-3-11bp inverted repeat motif and class 2 target promoters containing a single 11 bp motif. All 630 ChIP-exo peaks contain at least one motif, suggesting a global role for RsrR. However, the strongest targets are class 1 and include NAD(P)+ dependent enzymes, NAD(P)+ biosynthetic enzymes, the NADH and NADPH dehydrogenases and a putative NAD(P)+ binding regulator that is divergently transcribed from rsrR. Thus, our data suggest RsrR senses redox changes in the cell and has a primary role in regulating NAD(P)H metabolism. ER -