Transcription factor MrpC binds to promoter regions of hundreds of developmentally-regulated genes in Myxococcus xanthus

Robinson, Mark; Son, Bongjun; Kroos, David; Kroos, Lee

doi:10.1186/1471-2164-15-1123

Cited by 35 publications

(70 citation statements)

References 121 publications

(279 reference statements)

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“…In addition to the dev promoter and the four fmg promoters mentioned above, ChIP-seq analysis of cells that had formed nascent fruiting bodies revealed 1,608 putative MrpC-binding sites, and when 15 of these were tested for cooperative binding of MrpC2 and FruA, there was evidence for cooperative binding in 13 cases (62). These include sites near the 5= ends of genes important for development, such as genes that code for protein kinases or transcription factors, and genes involved in signal production, spore formation, and motility.…”

Section: Discussionmentioning

confidence: 99%

“…3) very similar to a consensus sequence for MrpC binding (TGTYN 8 RAC). The consensus sequence was identified by bioinformatic analysis of sequences bound by MrpC, as determined by chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) of M. xanthus that had formed nascent fruiting bodies (62). Mutations M2A and M2B have changes in the middle (i.e., the nonspecific N 8 part) of the sequence matching the consensus.…”

Section: Binding Of a Protein In A Fraction From Developing M Xanthumentioning

confidence: 99%

“…MrpC2 appears to activate the transcription of fruA (42). MrpC2 appeared to have higher DNA-binding activity than MrpC (45), but the two forms of the protein had similar DNA-binding activity for the fruA promoter region in a recent study (62). Since MrpC2 cannot be phosphorylated, it might play an important role in escaping negative regulation by the protein kinase cascade during development (45).…”

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Combinatorial Regulation of thedevOperon by MrpC2 and FruA during Myxococcus xanthus Development

et al. 2014

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Proper expression of the dev operon is important for normal development of Myxococcus xanthus. When starved, these bacteria coordinate their gliding movements to build mounds that become fruiting bodies as some cells differentiate into spores. Mutations in the devTRS genes impair sporulation. Expression of the operon occurs within nascent fruiting bodies and depends in part on C signaling. Here, we report that expression of the dev operon, like that of several other C-signal-dependent genes, is subject to combinatorial control by the transcription factors MrpC2 and FruA. A DNA fragment upstream of the dev promoter was bound by a protein in an extract containing MrpC2, protecting the region spanning positions ؊77 to ؊54. Mutations in this region impaired binding of purified MrpC2 and abolished developmental expression of reporter fusions. The association of MrpC2 and/or its longer form, MrpC, with the dev promoter region depended on FruA in vivo, based on chromatin immunoprecipitation analysis, and purified FruA appeared to bind cooperatively with MrpC2 to DNA just upstream of the dev promoter in vitro. We conclude that cooperative binding of the two proteins to this promoter-proximal site is crucial for dev expression. 5= deletion analysis implied a second upstream positive regulatory site, which corresponded to a site of weak cooperative binding of MrpC2 and FruA and boosted dev expression 24 h into development. This site is unique among the C-signal-dependent genes studied so far. Deletion of this site in the M. xanthus chromosome did not impair sporulation under laboratory conditions. Myxococcus xanthus is a Gram-negative bacterium that undergoes multicellular development (1). Upon starvation on a solid surface, cells coordinate their movements to build mounds that contain thousands of cells. Within these nascent fruiting bodies, some cells differentiate from rods to ovoid spores. Other cells lyse during the developmental process or remain outside fruiting bodies as peripheral rods. The spores remain viable during prolonged starvation and resist environmental insults. Under favorable conditions, spores germinate, producing rod-shaped cells capable of growth and division.The developmental process of M. xanthus provides an attractive model to study signaling and gene regulatory mechanisms (1). Here, we focus on regulation of the dev operon in response to extracellular C signaling. The dev locus was identified by two transposon insertions that created reporter fusions induced during development (2, 3). Expression from the fusions was reduced in a csgA mutant incapable of C signaling (4). The transposon insertions in the dev locus prevented darkening of nascent fruiting bodies and reduced sporulation Ͼ100-fold (3, 5). The sporulation defect can be accounted for by the observation that a dev mutant fails to express the ⍀7536 locus (6), the site of the exo operon, whose products are necessary for spore formation (7). How the products of the dev operon regulate the expression of the exo operon is unknown. The dev op...

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Section: Discussionmentioning

confidence: 99%

Section: Binding Of a Protein In A Fraction From Developing M Xanthumentioning

confidence: 99%

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Combinatorial Regulation of thedevOperon by MrpC2 and FruA during Myxococcus xanthus Development

et al. 2014

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“…Genetic evidence suggests that C-signal activates the transcription factor FruA (depicted as FruA* in Figure 2), facilitating aggregation [18–20], but many questions remain about C-signaling (Box 1). FruA* and the transcription factor MrpC (the output of the Mrp module) are believed to regulate late genes important for completion of the developmental process [21, 22] (Figure 2). As explained next, the EBP cascade module impacts many steps in the GRN (Figure 2).…”

Section: Overview Of the Grn Governing Myxococcus Developmentmentioning

confidence: 99%

Highly Signal-Responsive Gene Regulatory Network Governing Myxococcus Development

Kroos

2017

Trends in Genetics

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The bacterium Myxococcus xanthus undergoes multicellular development when starved. Thousands of cells build mounds in which some differentiate into spores. This remarkable feat and the genetic tractability of Myxococcus provide a unique opportunity to understand evolution of gene regulatory networks (GRNs). Recent work has revealed a GRN involving interconnected cascades of signal-responsive transcriptional activators. Initially, starvation-induced intracellular signals direct changes in gene expression. Subsequently, self-generated extracellular signals provide morphological cues that regulate certain transcriptional activators. However, signals for many of the activators remain to be discovered. A key insight is that activators often work combinatorially, allowing signal integration. The Myxococcus GRN differs strikingly from those governing sporulation of Bacillus and Streptomyces, suggesting Myxococcus evolved a highly signal-responsive GRN to enable complex multicellular development.

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“…Since the transcription of fruA depends on MrpC (15), and the two transcription factors bind DNA promoter regions cooperatively to regulate the transcription of many genes (16)(17)(18)(19)(20), including the dev operon (9), we also measured the MrpC level during development of the ΔdevT mutants. Consistent with an earlier blockage of the developmental program in the original ΔdevT408 -502 mutant, MrpC accumulation was reduced relative to wild-type DK1622 (Fig.…”

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The dev Operon Regulates the Timing of Sporulation during Myxococcus xanthus Development

Rajagopalan

Kroos

2017

J Bacteriol

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Myxococcus xanthus undergoes multicellular development when starved. Thousands of rod-shaped cells coordinate their movements and aggregate into mounds in which cells differentiate into spores. Mutations in the dev operon impair development. The dev operon encompasses a clustered regularly interspaced short palindromic repeat-associated (CRISPR-Cas) system. Null mutations in devI, a small gene at the beginning of the dev operon, suppress the developmental defects caused by null mutations in the downstream devR and devS genes but failed to suppress defects caused by a small in-frame deletion in devT. We provide evidence that the original mutant has a second-site mutation. We show that devT null mutants exhibit developmental defects indistinguishable from devR and devS null mutants, and a null mutation in devI suppresses the defects of a devT null mutation. The similarity of DevTRS proteins to components of the CRISPR-associated complex for antiviral defense (Cascade), together with our molecular characterization of dev mutants, support a model in which DevTRS form a Cascade-like subcomplex that negatively autoregulates dev transcript accumulation and prevents DevI overproduction that would strongly inhibit sporulation. Our results also suggest that DevI transiently inhibits sporulation when regulated normally. The mechanism of transient inhibition may involve MrpC, a key transcription factor, whose translation appears to be weakly inhibited by DevI. Finally, our characterization of a devI devS mutant indicates that very little exo transcript is required for sporulation, which is surprising since Exo proteins help form the polysaccharide spore coat.IMPORTANCE CRISPR-Cas systems typically function as adaptive immune systems in bacteria. The dev CRISPR-Cas system of M. xanthus has been proposed to prevent bacteriophage infection during development, but how dev controls sporulation has been elusive. Recent evidence supported a model in which DevR and DevS prevent overproduction of DevI, a predicted 40-residue inhibitor of sporulation. We provide genetic evidence that DevT functions together with DevR and DevS to prevent DevI overproduction. We also show that spores form about 6 h earlier in mutants lacking devI than in the wild type. Only a minority of natural isolates appear to have a functional dev promoter and devI, suggesting that a functional dev CRISPR-Cas system evolved recently in niches where delayed sporulation and/or protection from bacteriophage infection proved advantageous.KEYWORDS CRISPR-Cas, Myxococcus xanthus, bacterial development, dev operon, gene regulation, signaling, sporulation M yxococcus xanthus is a Gram-negative soil bacterium that exhibits social behaviors (1). In nature, cells of M. xanthus move in groups, feeding on prey bacteria and organic detritus. When starved, thousands of cells aggregate to form mounds that mature into fruiting bodies as rod-shaped cells differentiate into dormant ovoid spores.

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Transcription factor MrpC binds to promoter regions of hundreds of developmentally-regulated genes in Myxococcus xanthus

Cited by 35 publications

References 121 publications

Combinatorial Regulation of thedevOperon by MrpC2 and FruA during Myxococcus xanthus Development

Combinatorial Regulation of thedevOperon by MrpC2 and FruA during Myxococcus xanthus Development

Highly Signal-Responsive Gene Regulatory Network Governing Myxococcus Development

The dev Operon Regulates the Timing of Sporulation during Myxococcus xanthus Development

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