Research Description:
We study mechanisms of regulation by the histone-like nucleoid-structuring protein H-NS in commensal and pathogenic Escherichia coli. Specifically, we focus on mechanisms of de-repression by the transcriptional regulator LeuO and by FixJ/LuxR-type transcription factors such as BglJ-RcsB and others, and their role in regulatory networks controlling pathogenicity. In addition, we analyze the interdependence of repression by H-NS and the rate of transcription.
H-NS is an pleiotropic regulator and an architectural protein of the enterobacterial chromosome (the nucleoid), and it is important for silencing of loci acquired by horizontal gene transfer and for bacterial fitness. H-NS binds as dimer to specific nucleation sites located within an AT-rich sequence context, and then forms extended complexes by polymerization along the DNA ('stiffening') and by building DNA-H-NS-DNA bridges ('bridging'). Formation of H-NS-DNA complexes next to promoters represses transcription by occluding RNA polymerase or, as shown in some cases, by trapping RNA polymerase at the promoter.
Repression by H-NS can be relieved locus-specifically by various mechanisms. Most commonly, binding of specific transcriptional regulators compete with H-NS or restructure the H-NS-nucleoprotein complex. Other mechanisms include locus specific changes of the DNA structure (bending), enhancement of the transcription rate, and possibly direct modulation of the H-NS activity by changes of the physiological conditions.
The LysR-type transcription factor LeuO and the heterodimer of the LuxR-type transcription factors BglJ-RcsB are known H-NS antagonists. These transcription factors are part of a regulatory network, related to control of bacterial virulence.
Group Members:
Katrin Dreck (Ph.D. student since 11/2009)
Derk Pannen (Ph.D. student since 01/2012)
Thomas Stratmann (research associate, Ph.D. 01/2009 - 04/2012)
Publications:
Stratmann, T., Pul, Ü., Wurm, R., Wagner, R., and Schnetz, K. (2012).
RcsB-BglJ activates the Escherichia coli leuO gene, encoding an H-NS antagonist and pleiotropic regulator of virulence determinants.
Mol Microbiol 83, 1109–1123.
Kavalchuk, K., Madhusudan, S., and Schnetz, K. (2012).
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RNase III initiates rapid degradation of proU mRNA upon hypo-osmotic stress in Escherichia coli.
RNA Biology 9, 98-109.
Perfeito, L., Ghozzi, S., Berg, J., Schnetz, K., and Lässig, M. (2011)
Nonlinear Fitness Landscape of a Molecular Pathway.
PLoS Genet 7, e1002160.
Venkatesh G.R., Kembou Koungni F.C., Paukner A., Stratmann T., Blissenbach B., and Schnetz K. (2010)
BglJ-RcsB heterodimers relieve repression of the Escherichia coli bgl operon by H-NS.
J. Bacteriol. 192, 6456-6464
Westra, E.R., Pul, U., Heidrich, N., Jore, M.M., Lundgren, M., Stratmann, T., Wurm, R., Raine, A., Mescher, M.,
van Heereveld L., Mastop, M., Wagner, E. G., Schnetz, K., van der Oost, J., Wagner, R., and Brouns, S. J. (2010)
H-NS-mediated repression of CRISPR-based immunity in Escherichia coli K12 can be relieved by the transcription activator LeuO.
Mol Microbiol 77, 1380-1393.
Neelakanta G., Sankar S.T., and Schnetz K. (2009)
Characterization of a β-glucoside operon (bgc) prevalent in septicemic and uropathogenic Escherichia coli.
Appl. Environ. Microbiol. 75,2284-2293.
Sankar S.T., Neelakanta G., Sangal V., Plum G., Achtman M., and Schnetz K. (2009)
Fate of the H-NS repressed bgl operon in evolution of Escherichia coli.
PLoS Genetics 5:e1000405.
Schnetz K. (2008)
Fine-tuned growth phase control of dps, encoding a DNA protection protein, by FIS and H-NS.
Mol. Microbiol. 68(6):1345-1347. Epub 2008 Apr 21.
Li G., Ewers C., Laturnus C., Diehl I., Alt K., Dai J., Antao E.M., Schnetz K., Wieler L.H. (2008)
Characterization of a yjjQ mutant of avian pathogenic Escherichia coli (APEC).
Microbiology 154:1082-1093.
Radde N., Gebert J., Faigle U., Schrader R., and Schnetz K. (2008)
Modeling feedback loops in the H-NS mediated regulation of the Escherichia coli bgl operon.
J. Theor. Biol. 250(2):298-306. Epub 2007 Nov 5. doi:10.1016/j.jtbi.2007.09.033.
Stratmann T., Madhusudan S., and Schnetz K. (2008)
Regulation of the yjjQ-bglJ operon encoding LuxR-type transcription factors and the divergent yjjP gene by H-NS and LeuO.
J. Bacteriol., 190(3):926-935. Epub 2007 Nov 30.
Nagarajavel V., Madhusudan S., Dole S., Rahmouni A.R., and Schnetz K. (2007)
Repression by binding of H-NS within the transcription unit.
J. Biol. Chem. 282 (32):23622-23630, 2007.
Wolf, T., Janzen, W., Blum, C. and Schnetz, K. (2006)
Differential dependence of StpA on H-NS in auto-regulation of stpA and in regulation of bgl.
J. Bacteriol 188 (19): 6728-6838.
Madhusudan, S., Paukner, A., Klingen, Y. and Schnetz, K. (2005)
Independent regulation of H-NS-mediated silencing of the bgl operon at two levels: upstream by BglJ and LeuO and downstream by DnaKJ.
Microbiology 151: 3349-3359.
Dole, S., Klingen, Y., Nagarajavel, V., and Schnetz, K. (2004)
The protease Lon and the RNA-binding protein Hfq
reduce silencing of the E.coli bgl operon by H-NS.
J. Bact. 186, 2708-2716.
Dole, S., Nagarajavel, V., and Schnetz, K. (2004)
The histone-like nucleoid structuring protein H-NS represses
the Escherichia coli bgl operon downstream of the promoter.
Mol. Microbiol. 52, 589-600.
Schnetz, K. (2002)
Silencing of the Escherichia coli bgl operon by RpoS requires Crl.
Microbiology 148, 2573-2578.
Dole, S., Kühn, S., and Schnetz, K. (2002)
Post-transcriptional enhancement of Escherichia coli bgl operon silencing
by limitation of BglG-mediated antitermination at low transcription rates.
Mol. Microbiol. 43, 217-226.
Caramel, A. and Schnetz, K. (2000)
Antagonistic control of the E. coli bgl promoter by FIS and CAP in vitro.
Mol. Microbiol. 36, 85-92.
Caramel, A. and Schnetz, K. (1998)
Lac and Lambda repressor relieve silencing of the Escherichia coli bgl promoter.
Activation by alteration of a repressing nucleoprotein complex.
J. Mol. Biol. 284, 875-883.
Schnetz, K. and Wang, J.C. (1996)
Silencing of the Escherichia coli bgl promoter: Effects of template supercoiling and cell
extracts on promoter activity in vitro.
Nucleic. Acids. Res. 24, 2422-2429.
Koch, S., Sutrina, S.L., Wu, L.-F., Reizer, J.,
Schnetz, K., Rak, B., and Saier, M.H., Jr. (1996)
Identification of a site in the phosphocarrier protein, HPr, which influences its interactions
with sugar permeases of the bacterial phosphotransferase system:
kinetic analyses employing site-specific mutants.
J. Bacteriol. 178, 1126-1133.
Schnetz, K., Stülke, J., Gertz, S., Krüger, S., Krieg, M., Hecker, M., and Rak, B. (1996)
LicT, a Bacillus subtilis transcriptional antiterminator protein of the BglG family.
J. Bacteriol. 178, 1971-1979.
Schnetz, K. (1995)
Silencing of Escherichia coli bgl promoter by flanking sequence elements.
EMBO J. 14, 2545-2550.
Ph.D. Thesis
Thomas Stratmann (2012) Transcriptional control of the H-NS antagonists LeuO and RcsB-BglJ in Escherichia coli
Kanstantsin Kavalchuk (2011) Osmoregulation of the proU operon at a post-transcriptional level in Escherichia coli
Raja Venkatesh G. (2010) The Analysis of the interaction of LuxR-type transcription factors BglJ and RcsB in Escherichia coli
Sabari Sankar Thirupathy (2008) The evolution of silent β,D-glucoside systems in Escherichia coli
Madhusudan S. (2007) The mechanism and modulation of H-NS mediated repression in Escherichia coli
Andreas Paukner (2007) Ein Regulationsnetzwerk aus H-NS und den Antireperessoren BglJ und LeuO
Nagarajavel V. (2007) H-NS mediated repression of the E.coli bgl and proU operons
Neelakanta, Girish (2005) Genome variations in commensal and pathogenic E.coli
Dole, Sudhanshu (2001) Multiple level regulation of the Escherichia coli bgl operon
Caramel, Angela (1999) On the activation and regulation of the silent Escherichia coli bgl promoter
Diploma Thesis
Kretschmer, Andreas (2010) Wechselbeziehung zwischen Transkription und Repression durch die Nucleoid-assoziierten Proteine H-NS und StpA
Bouchara, Idriss (2009) Zur Transkriptionsregulation durch den globalen Regulator H-NS in Escherichia coli
Blissenbach, Birgit (2008) Antagonistische Regulation des yjjP-yjjQ-bglJ-Locus durch H-NS und den Transkriptionsfaktor LeuO
Fabisch, Maria (2008) Wechselwirkung von Transkriptionsfaktoren des LuxR-Typs in Escherichia coli
Kembou Kougni, Frant Carlot (2007) Interaktion der Transkriptionsfaktoren BglJ und YjjQ von Escherichia coli mit RcsB
Kakanj, Parisa (2005) Die Regulation des bgl-Operons von E.coli durch Hfq
Wolf, Tinka (2004) Zur Funktion der homologen Proteine H-NS und StpA in E.coli
Thiemann, Markus (2003) Zur Autoregulation des Antiterminators BglG von E.coli
Klingen, Yvonne (2001) Zur Rolle der Protease Lon im Silencing des E.coli bgl Operons
Borsos, Karolj (2000) Zur Regulation des bgl Promotors durch FIS
Bachelor Thesis
Schwarzer, Robin (2011) Untersuchungen über den positiven feedback-loop der Transkriptionsfaktoren BglJ und LeuO in Escherichia coli
Basfeld, Alrun (2011) Analyse synthetischer H-NS Bindestellen und eines Promotorsystems in Escherichia coli
Öztürk, Selman (2010) Homo- und Heterodimerisierung des Transkriptionsfaktors RcsB in E. coli
Scholz, Paul (2009) Regulation des leuO Locus in Escherichia coli
Antunes, Andre (2008) Role of the small regulatory RNA SgrS in regulation of the Escherichia coli bgl operon
Muhr, Merlin (2008) Analysis of repression by binding of H-NS within the transcription unit
Klemme, Sonja (2007) Kartierung der Interaktionsdomänen der LuxR-Typ Transkriptionsfaktoren RcsA, RcsB, YjjQ and BglJ in Escherichia coli
Moll, Lorna (2006) Zur Regulation des yjjP-yjjQ-bglJ Locus von Escherichia coli
durch H-NS und LeuO
Staatsexamen
Pannen, Derk (2011) Analyse der Homo- und Heterodimerisierung des Transkriptionsfaktors RcsB in Escherichia coli
Stratmann, Thomas (2007) Regulation des yjjP-yjjQ-bglJ-Locus von Escherichia coli durch H-NS und LeuO
Blum, Corinna (2005) Analyse von Mutanten des Histon-ähnlichen Proteins H-NS
Janzen, Wiebke (2005) Regulation des stpA-Gens und Wechselwirkung mit dem Histon-ähnlichen Protein H-NS
Nix, Annette (2001) Zur Regulation des bgl Operons von Escherichia coli:
Aktiviert das Antiterminatorprotein BglG die Translation seiner mRNA?
Former Members:
04/2008 - 11/2011 Kanstantsin Kavalchuk (Ph.D. student)
04/2011 - 07/2011 Robin Schwarzer (Bachelor student)
10/2010 - 01/2011 Alrun Basfeld (Bachelor Student)
10/2008 - 12/2010 Lilia Perfeito (PostDoc)
11/2009 - 09/2010 Andreas Kretschmer (Diploma Student)
04/2010 - 08/2010 Selman Öztürk (Bachelor Student)
04/2007 - 04/2010 Raja Venkatesh G.(Ph.D. student)
02/2008 - 09/2009 Birgit Blissenbach (Diploma Student and Research assistent)
12/2008 - 09/2009 Idriss Bouchara (Diploma student)
05/2009 - 08/2009 Paul Scholz (Bachelor Student)
03/2008 - 09/2008 Merlin Muhr (Bachelor student/Research Assistent)
04/2008 - 07/2008 Andre Antunes (Bachelor Student)
03/2005 - 05/2008 Kathleen Plamper (Technician)
08/2007 - 06/2008 Maria Fabisch (Diploma student)
04/2004 - 02/2008 Sabari Sankar Thirupathy (Ph.D. student)
04/2003 - 11/2007 Madhusudan S. (Ph.D. student)
06/2007 - 09/2007 Thomas Stratmann (SekII Student)
05/2007 - 08/2007 Sonja Klemme (Bachelor Student)
10/2002 - 07/2007 Andreas Paukner (Ph.D. student)
04/2002 - 02/2007 Nagarajavel V. (Ph.D. student)
03/2006 - 01/2007 Frant Carlot Kembou Kougni (Diploma Student)
12/2003 - 08/2006 Tinka Wolf (Diploma Student and Research Assistant)
05/2006 - 08/2006 Lorna Moll (Bachelor Student)
03/2003 - 02/2006 Doris Renz (Technician)
12/2004 - 03/2005 Wiebke Janzen (SekII Student)
12/2004 - 03/2005 Corinna Blum (SekII Student)
06/2001 - 02/2005 Girish Neelakanta (Ph.D. student)
03/2004 - 12/2004 Parisa Kakanj (Diploma Student)
03/2003 - 12/2003 Markus Thiemann (Diploma Student)
01/1998 - 03/2003 Sandra Kühn (Technician)
01/2001 - 05/2002 Yvonne Klingen (Diploma Student and Research Assistent)
10/1997 - 02/2002 Sudhanshu Dole (Ph.D. student)
04/2001 - 06/2001 Annette Nix (SekII Student)
08/1999 - 05/2001 Karolj Borsos (Diploma Student)
11/1998 - 12/2000 Helmut Niersbach (Postdoc)
08/1995 - 03/2000 Angela Caramel (Ph.D. student and Postdoc)
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