The Mechanism by which DNA Adenine Methylase and PapI Activate the Pap Epigenetic Switch

Hernday, Aaron D.; Braaten, Bruce A.; Low, David A.

doi:10.1016/s1097-2765(03)00383-6

Cited by 124 publications

(221 citation statements)

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“…However, previous attempts to detect the DNA-binding activity of PapI independent of Lrp have been inconclusive. 7,9 In this report, we present the solution structure and backbone dynamics of PapI. Our results show that PapI is indeed a winged helix-turn-helix protein.…”

Section: Introductionmentioning

confidence: 82%

“…9 Recent results from the Low laboratory have clearly demonstrated that the specificity of the PapI effect on the binding of Lrp to individual pap binding sites is centered on the two GATC sites located at subsites 2 and 5. 9 The Low laboratory used competitive band shift assays to monitor the binding of Lrp to each of the six pap binding sites in the presence and absence of PapI.…”

Section: Introductionmentioning

confidence: 99%

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Solution Structure of Escherichia coli PapI, a Key Regulator of the Pap Pili Phase Variation

Kawamura

Zhou

et al. 2007

Journal of Molecular Biology

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Pyelonephritis-associated pili (pap) allow uropathogenic Escherichia coli to bind to epithelial cells and play an important role in urinary tract infection. Expression of pap pili is controlled by a phasevariation mechanism, based on the two distinct heritable states that are the result of adenine N6-methylation in either of the two GATC sequences in its regulatory region. Methylation status of these two sequences is sensed by the action of two proteins, Lrp and PapI, and they play a central role in determining pap pili gene expression in both phase-ON and phase-OFF cells. We used modern nuclear magnetic resonance techniques to determine the solution structure and backbone dynamics of PapI. We found its overall fold closely resembles that of the winged helix-turn-helix family of DNA-binding proteins. We also determined that PapI possesses its own DNA-binding activity, albeit non-sequence specific, independent of Lrp. PapI appears to bind to DNA with a K d in the 10 µM range. Possible mechanisms by which PapI might participate in the regulation of the pap operon are discussed in light of these new findings.

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Section: Introductionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Solution Structure of Escherichia coli PapI, a Key Regulator of the Pap Pili Phase Variation

Kawamura

Zhou

et al. 2007

Journal of Molecular Biology

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“…Epigenetic phenomena include prions, in which protein structure is heritably transmitted (223,231,235,259); genomic imprinting, characterized by monoallelic repression of maternally or paternally inherited genes (52,84,128,195,213); histone modification, such as methylation of lysines by histone phase methyltransferases (MTases) that maintain active and silent chromatin states (132,273); and DNA methylation patterns formed as a result of inhibition of methylation of specific DNA bases by protein binding (29,41,118,262,263). Each of these phenomena involve self-perpetuating states, be they protein or DNA related (116,155,(230)(231)(232), and the particular state that the molecule is in affects gene expression.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Gene Regulation in the Bacterial World

Casadesús

Low

2006

Microbiol Mol Biol Rev

567

562

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SUMMARY Like many eukaryotes, bacteria make widespread use of postreplicative DNA methylation for the epigenetic control of DNA-protein interactions. Unlike eukaryotes, however, bacteria use DNA adenine methylation (rather than DNA cytosine methylation) as an epigenetic signal. DNA adenine methylation plays roles in the virulence of diverse pathogens of humans and livestock animals, including pathogenic Escherichia coli, Salmonella, Vibrio, Yersinia, Haemophilus, and Brucella. In Alphaproteobacteria, methylation of adenine at GANTC sites by the CcrM methylase regulates the cell cycle and couples gene transcription to DNA replication. In Gammaproteobacteria, adenine methylation at GATC sites by the Dam methylase provides signals for DNA replication, chromosome segregation, mismatch repair, packaging of bacteriophage genomes, transposase activity, and regulation of gene expression. Transcriptional repression by Dam methylation appears to be more common than transcriptional activation. Certain promoters are active only during the hemimethylation interval that follows DNA replication; repression is restored when the newly synthesized DNA strand is methylated. In the E. coli genome, however, methylation of specific GATC sites can be blocked by cognate DNA binding proteins. Blockage of GATC methylation beyond cell division permits transmission of DNA methylation patterns to daughter cells and can give rise to distinct epigenetic states, each propagated by a positive feedback loop. Switching between alternative DNA methylation patterns can split clonal bacterial populations into epigenetic lineages in a manner reminiscent of eukaryotic cell differentiation. Inheritance of self-propagating DNA methylation patterns governs phase variation in the E. coli pap operon, the agn43 gene, and other loci encoding virulence-related cell surface functions.

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“…Phenotypic heterogeneity among isogenic cells has been investigated in natural systems (Novick and Weiner 1957;Ferrell and Machleder 1998;Hernday et al 2003;Maamer and Dubnau 2005) and by theoretical studies (Ferrell 2002). Simulations have shown that in Xuctuating conditions dynamic heterogeneity can enhance Wtness (Thattai and van Oudenaarden 2004) and is subject of natural selection (Fraser et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Heterogeneity in expression of the Escherichia coli colicin K activity gene cka is controlled by the SOS system and stochastic factors

et al. 2007

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Phenotypic diversity provides populations of prokaryotic and eukaryotic organisms with the Xexibility required to adapt to and/or survive environmental perturbations. Consequently, there is much interest in unraveling the molecular mechanisms of heterogeneity. A classical example of heterogeneity in Escherichia coli is the subset (3%) of the population that expresses the colicin K activity gene (cka) upon nutrient starvation. Here, we report on the mechanism underlying this variable response. As colicin synthesis is regulated by the LexA protein, the central regulator of the SOS response, we focused on the role of LexA and the SOS system in the variable cka expression. Real-time RT-PCR showed that the SOS system, without exogenous DNA damage, induces moderate levels of cka expression. The use of cka-gfp fusions demonstrated that modiWcation of the conserved LexA boxes in the cka promoter region aVected LexA binding aYnity and the percentage of cka-gfp expressing cells in the population. A lexA-gfp fusion showed that the lexA gene is highly expressed in a subset of bacteria.Furthermore, cka-gfp fusions cloned into higher copy plasmid vectors increased the percentage of cka-gfp positive bacteria. Together, these results indicate that the bistability in cka expression in the bacterial population is determined by (1) basal SOS activity, (2) stochastic factors and possibly (3) the interplay of LexA dimers at cka operator. Other LexA regulated processes could exhibit similar regulation.

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The Mechanism by which DNA Adenine Methylase and PapI Activate the Pap Epigenetic Switch

Cited by 124 publications

References 40 publications

Solution Structure of Escherichia coli PapI, a Key Regulator of the Pap Pili Phase Variation

Solution Structure of Escherichia coli PapI, a Key Regulator of the Pap Pili Phase Variation

Epigenetic Gene Regulation in the Bacterial World

Heterogeneity in expression of the Escherichia coli colicin K activity gene cka is controlled by the SOS system and stochastic factors

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