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Regulatory interplay of cell cycle transcription factors in compartmentalized Caulobacter cells

English title Regulatory interplay of cell cycle transcription factors in compartmentalized Caulobacter cells
Applicant Viollier Patrick
Number 143660
Funding scheme Project funding (Div. I-III)
Research institution Dépt Microbiologie et Médecine Moléculaire Faculté de Médecine Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Experimental Microbiology
Start/End 01.10.2012 - 30.09.2015
Approved amount 567'000.00
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All Disciplines (5)

Discipline
Experimental Microbiology
Molecular Biology
Cellular Biology, Cytology
Embryology, Developmental Biology
Genetics

Keywords (9)

transcription factor; ChIP-SEQ; motility; compartmentalization; G1-phase; asymmetric division; cell-cycle control; pho system; Caulobacter

Lay Summary (English)

Lead
Lay summary

The defining event in cytokinesis (cell division) is the act of compartmentalization in which the pre-divisional cell is split into two chambers that are physically separated by a diffusion barrier. In many different cell types cytokinesis is programmed to be asymmetric, yielding two daughter cells with dissimilar sizes, shapes, morphologies and/or functions. The importance of cell specialization by asymmetric division in eukaryotic development underscores the need for a rigorous investigation, at the most fundamental level,  of the asymmetric division process. The fact that many bacterial cells divide asymmetrically and are genetically very tractable, makes them a powerful primitive model system to  dissect the regulatory principles underlying asymmetric division. Asymmetric divisions are particularly pervasive in the alpha-protebacterial lineage, which includes the synchronizable bacterium Caulobacter crescentus. The synchronzability of C. crescentus has enabled whole-genome transcriptional analyses during the asymmetric cell division cycle, revealing that in one daughter chamber the transcriptional program for the non-replicating (G1 phase) state is active, while in the other daughter the program for the replicative (S-phase) state is implemented. How these two dissimilar transcriptional programs are activated is not fully understood and the subject of this work. We identified factors that control these programs and we will further explore the genetic relationships among these factors to illuminate how the individual regulatory layers integrate into a robust system for compartment-specific activation of the two transcriptional programs. Included in our analysis is a phosphate-sensory system that interacts genetically with a master transcriptional regulator of the cell cycle, as well as a conserved transcription factor that controls the expression of virulence or symbiosis genes in relatives of C. crescentus. We will characterize the functional interplay amongst these transcriptional regulators in wild-type and mutant proteins using state-of-the-art genomic, classical genetic and biochemical methods.

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
An Adaptor Hierarchy Regulates Proteolysis during a Bacterial Cell Cycle
Joshi Kamal Kishore, Berge Matthieu, Radhakrishnan Sunish Kumar, Viollier Patrick Henri, Chien Peter (2015), An Adaptor Hierarchy Regulates Proteolysis during a Bacterial Cell Cycle, in CELL, 163(2), 419-431.
Cell Cycle Control by the Master Regulator CtrA in Sinorhizobium meliloti
De Nisco Nicole J., Ferri Lorenzo, Penterman Jon, Fioravanti Antonella, Brilli Matteo, Mengoni Alessio, Bazzicalupo Marco, Viollier Patrick H., Walker Graham C., Biondi Emanuele G. (2015), Cell Cycle Control by the Master Regulator CtrA in Sinorhizobium meliloti, in PLOS GENETICS, 11(5), 1-24.
Convergence of Alarmone and Cell Cycle Signaling from Trans-Encoded Sensory Domains.
Sanselicio Stefano, Viollier Patrick (2015), Convergence of Alarmone and Cell Cycle Signaling from Trans-Encoded Sensory Domains., in MBio, 6(5), 1-10.
Topological control of the Caulobacter cell cycle circuitry by a polarized single-domain PAS protein
Sanselicio Stefano, Berge Matthieu, Theraulaz Laurence, Radhakrishnan Sunish Kumar, Viollier Patrick H. (2015), Topological control of the Caulobacter cell cycle circuitry by a polarized single-domain PAS protein, in NATURE COMMUNICATIONS, 6, 1-14.
Versatility of global transcriptional regulators in alpha-Proteobacteria: from essential cell cycle control to ancillary functions
Murray Sean R., Viollier Patrick H. (2015), Versatility of global transcriptional regulators in alpha-Proteobacteria: from essential cell cycle control to ancillary functions, in FEMS MICROBIOLOGY REVIEWS, 39(1), 120-133.
A Cell Cycle and Nutritional Checkpoint Controlling Bacterial Surface Adhesion
Fiebig Aretha, Herrou Julien, Fumeaux Coralie, Radhakrishnan Sunish K., Viollier Patrick H., Crosson Sean (2014), A Cell Cycle and Nutritional Checkpoint Controlling Bacterial Surface Adhesion, in PLOS GENETICS, 10(1), 1-14.
Cell cycle constraints on capsulation and bacteriophage susceptibility
Ardissone Silvia, Fumeaux Coralie, Bergé Matthieu, Beaussart Audrey, Théraulaz Laurence, Radhakirishnan Sunish, Viollier Patrick (2014), Cell cycle constraints on capsulation and bacteriophage susceptibility, in Elife, 1-30.
Cell cycle transition from S-phase to G1 in Caulobacter is mediated by ancestral virulence regulators
Fumeaux Coralie, Radhakrishnan Sunish Kumar, Ardissone Silvia, Theraulaz Laurence, Frandi Antonio, Martins Daniel, Nesper Jutta, Abel Soeren, Jenal Urs, Viollier Patrick H. (2014), Cell cycle transition from S-phase to G1 in Caulobacter is mediated by ancestral virulence regulators, in NATURE COMMUNICATIONS, 5, 1-14.
Computational and Genetic Reduction of a Cell Cycle to Its Simplest, Primordial Components
Murray Sean M., Panis Gael, Fumeaux Coralie, Viollier Patrick H., Howard Martin (2013), Computational and Genetic Reduction of a Cell Cycle to Its Simplest, Primordial Components, in PLOS BIOLOGY, 11(12), 1-16.
De- and repolarization mechanism of flagellar morphogenesis during a bacterial cell cycle (vol 27, pg 2049, 2013)
Davis Nicole J., Cohen Yaniv, Sanselicio Stefano, Fumeaux Coralie, Ozaki Shogo, Luciano Jennifer, Guerrero-Ferreira Ricardo C., Wright Elizabeth R., Jenal Urs, Viollier Patrick. H. (2013), De- and repolarization mechanism of flagellar morphogenesis during a bacterial cell cycle (vol 27, pg 2049, 2013), in GENES & DEVELOPMENT, 27(20), 2292-2292.
DNA Binding of the Cell Cycle Transcriptional Regulator GcrA Depends on N6-Adenosine Methylation in Caulobacter crescentus and Other Alphaproteobacteria
Fioravanti Antonella, Fumeaux Coralie, Bompard Coralie, Brilli Matteo, Frandi Antonio, Castric Vincent, Villeret Vincent, Viollier Patrick H., Biondi Emanuele G. (2013), DNA Binding of the Cell Cycle Transcriptional Regulator GcrA Depends on N6-Adenosine Methylation in Caulobacter crescentus and Other Alphaproteobacteria, in PLOS GENETICS, 9(5), 1-16.
Complete Genome Sequence of Caulobacter crescentus Bacteriophage phi CbK
Panis Gael, Lambert Christophe, Viollier Patrick H. (2012), Complete Genome Sequence of Caulobacter crescentus Bacteriophage phi CbK, in JOURNAL OF VIROLOGY, 86(18), 10234-10235.

Associated projects

Number Title Start Funding scheme
141837 Functional genome analysis in a genetically intractable system: an interdisciplinary proof-of-concept study 01.09.2012 Sinergia
162716 Cell cycle-regulated surface structures in bacteria 01.10.2015 Project funding (Div. I-III)
127287 Molecular Basis of Cell Polarity and Division Control in Caulobacter crescentus 01.10.2009 Project funding (Div. I-III)

Abstract

In contrast to common belief, bacteria coordinate transcription of selected genes with cell cycle progression. One cell cycle event exploited for coordination is the physical act of cell compartmentalization that allows different transcriptional programs to be activated in each daughter cell compartment. Despite potentially being wide-spread in the a-proteobacteria and perhaps bacteria in general, the underlying molecular and regulatory mechanisms are not well understood. Here we identify and study the molecular determinants that control the activation of G1-phase (and repression of S-phase) promoters in the Caulobacter crescentus swarmer cell chamber after compartmentalization. C. crescentus is an ideal model system for such studies because of its genetic tractability and physical synchronizability. Moreover, at the end of each cell cycle, the closure of the division septum gives rise to two cellular chambers in which different transcriptional programs are activated. While in the swarmer cell chamber G1-phase specific promoters fire, in the stalked cell chamber S-phase promoters are activated. We identify(ied) factors that control this promoter selectivity and we will explore the genetic relationships among these determinants to understand how the individual regulatory layers integrate into a robust system for compartment-specific transcriptional activation. Included in this analysis is a phosphate sensory system that interacts genetically with a master transcriptional regulator of the cell cycle. We will characterize the functional interplay amongst these transcriptional regulators at the biochemical level with wild-type and mutant proteins. These experiments will primarily rely on a combination of powerful forward genetics, cutting-edge chromatin-immunoprecipitation/deep-sequencing (ChIP-SEQ) and in vitro competition experiment assayed by electrophoretic mobility shift and footprinting.
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