MrpC, a CRP/Fnr homolog, functions as a negative autoregulator during the Myxococcus xanthus multicellular developmental program

Abstract

MrpC, a member of the CRP/Fnr superfamily of transcriptional regulators, plays a key role in coordination of the multicellular developmental program in Myxococcus xanthus. Previous reports suggest MrpC is subject to complex regulation including activation by an unusual LonD-dependent proteolytic processing event that removes its unique N-terminal peptide, producing the isoform MrpC2. MrpC2 is proposed to positively autoregulate and regulate transcription of hundreds of genes necessary for both the aggregation and sporulation phases of the developmental program. We demonstrate here that mrpC expression bifurcates corresponding to different cell populations within the developmental program. During our analysis of regulatory events controlling this process, we demonstrate that MrpC2 is not an active isoform; rather, the N-terminal peptide is instead essential for MrpC function in vivo. We also demonstrate that MrpC is instead a negative autoregulator and represses its own expression by specifically competing with its enhancer binding protein, MrpB. These results provide an additional rare example of CRP/EBP coordinated regulation, and significantly revise the model for control of the central developmental transcriptional activator of the M. xanthus developmental program.