NDLI: Self-perpetuating epigenetic pili switches in bacteria

Content Provider	PubMed Central
Author	Aaron, Hernday Krabbe, Margareta Braaten, Bruce Low, David
Copyright Year	2002
Abstract	Bacteria have developed an epigenetic phase variation mechanism to control cell surface pili–adhesin complexes between heritable expression (phase ON) and nonexpression (phase OFF) states. In the pyelonephritis-associated pili (pap) system, global regulators [catabolite gene activator protein (CAP), leucine-responsive regulatory protein (Lrp), DNA adenine methylase (Dam)] and local regulators (PapI and PapB) control phase switching. Lrp binds cooperatively to three pap DNA binding sites, sites 1–3, proximal to the papBA pilin promoter in phase OFF cells, whereas Lrp is bound to sites 4–6 distal to papBA in phase ON cells. Two Dam methylation targets, GATCprox and GATCdist, are located in Lrp binding sites 2 and 5, respectively. In phase OFF cells, binding of Lrp at sites 1–3 inhibits methylation of GATCprox, forming the phase OFF DNA methylation pattern (GATCdist methylated, GATCprox nonmethylated). Binding of Lrp at sites 1–3 blocks pap pili transcription and reduces the affinity of Lrp for sites 4–6. Together with methylation of GATCdist, which inhibits Lrp binding at sites 4–6, the phase OFF state is maintained. We hypothesize that transition to the phase ON state requires DNA replication to dissociate Lrp and generate a hemimethyated GATCdist site. PapI and methylation of GATCprox act together to increase the affinity of Lrp for sites 4–6. Binding of Lrp at the distal sites protects GATCdist from methylation, forming the phase ON methylation pattern (GATCdist nonmethyated, GATCprox methylated). Lrp binding at sites 4–6 together with cAMP-CAP binding 215.5 bp upstream of the papBA transcription start, is required for activation of pilin transcription. The first gene product of the papBA transcript, PapB, helps maintain the switch in the ON state by activating papI transcription, which in turn maintains Lrp binding at sites 4–6.
Related Links	http://dx.doi.org/10.1073/pnas.182427199
Ending Page	16476
Page Count	7
Starting Page	16470
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	Suppl 4
Volume Number	99
Language	English
Publisher	The National Academy of Sciences
Publisher Date	2002-12-10
Access Restriction	Open
Rights Holder	The National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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