A combination of unusual transcription factors binds cooperatively to control Myxococcus xanthus developmental gene expression.
Myxococcus xanthus is a bacterium that undergoes multicellular development requiring coordinate regulation of multiple signaling pathways. One pathway governs aggregation and sporulation of some cells in a starving population and requires C-signaling, whereas another pathway causes programmed cell death and requires the MazF toxin. In response to starvation, the levels of the bifunctional transcription factor/antitoxin MrpC and its related proteolytic fragment MrpC2 are increased, inhibiting the cell death pathway via direct interaction of MrpC with MazF. Herein, we demonstrate that MrpC2 plays a direct role in the transcriptional response to C-signaling. We show that MrpC2 binds to sequences upstream of the C-signal-dependent fmgA promoter. These sequences are present in other C-signal-dependent promoter regions, indicating a general role for MrpC2 in developmental gene regulation. Association of MrpC and/or MrpC2 with the fmgA promoter region in vivo requires FruA, a protein that is similar to response regulators of 2-component signal transduction systems, but may not be phosphorylated. DNA binding studies showed that this association likely involves an unusual mechanism for a response regulator in which FruA and MrpC2 bind cooperatively to adjacent sites upstream of the fmgA promoter. We propose that this unusual mechanism of combinatorial control allows coordination of morphogenetic C-signaling with starvation signaling and cell death, determining spatiotemporal gene expression and cell fate.
Mittal
Sheenu
S
Cell and Molecular Biology Program, Michigan State University, East Lansing, MI 48824, USA.
Kroos
Lee
L
D001426:Bacterial Proteins / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D009024:Morphogenesis / Q000235:genetics; D016941:Myxococcus xanthus / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
D001426:Bacterial Proteins; C104848:FruA protein, Myxococcus xanthus; C433791:MrpC protein, Myxococcus xanthus; D014157:Transcription Factors