A computational study of bacterial gene regulation and adaptation ...

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IntroductionI.2. Basal players for transcription initiationIn bacteria, transcription initiation is a multi-step process (McClure 1985). It begins with therecruitment of the RNA polymerase (RNAP) holoenzyme, a complex of the multi-subunitcore RNAP enzyme and a !-factor, to a gene promoter. The !-factor is responsible forpromoter recognition and holoenzyme recruitment. It also allows the formation of thetranscriptional bubble or the open complex, which is a region of unwound DNA about 10 bpupstream of the transcription start site. Processive transcript elongation follows, althoughthere is strong evidence for extensive abortion of initiation events.Therefore, successful transcription requires several key components: (1) DNA sequence andtopology that would allow promoter recognition; (2) !-factors that can recognise promoters;(3) free RNAP for recruitment to the promoter concerned; and (4) finally transcription factors(TFs) which are proteins that enable condition-specific gene expression.I.2.1. RNA polymeraseThe multi-subunit DNA-dependent RNAP is responsible for all transcription in bacteria(Browning and Busby 2004). The active site of the enzyme is contained in two large subunitscalled " and "’. In addition, there are two identical copies of a smaller # subunit. This #subunit has two functional domains separated by a flexible linker: the N-terminal domain isnecessary for the assembly of the " and "’ subunits; the C-terminal domain can contact certainpromoter elements (see below) and also interacts with TFs. Finally, a less well-studied $subunit may not have a direct role in transcription. These together comprise the RNAP that iscapable of transcription but not promoter recognition. The latter is facilitated by proteinscalled !-factors (see below).An exponentially growing E. coli cell has about 5,000 - 6,000 RNAP molecules. 70-80% ofthese are utilised for transcribing a small minority of stable RNA genes, which leaves a verysmall population of RNAP molecules for the expression of nearly 2,000 protein-codingtranscriptional units. However, as not all transcriptional units need to be expressed all thetime, RNAP molecules can be directed to specific promoters depending on cellularrequirements. The choice of which genes to express under a given condition is controlled bya combination of different factors: (1) promoter-sequence strength; (2) 3D topology of the4
(A) Closed complex formationRNA polymerase Holoenzyme (not shown) binding to DNA directed by !-factor-mediatedpromoter recognitionUP element(flexible region)-35 -10!-factor(B) Open complex formationDNA unwinding around -10 region(C) Transcription elongationaccompanied by !-factor leaving the polymeraseholoenzymeRNA#C#N""’ subunit#C#N""’ subunitElongationSummary Figure. Summary of transcription initiation in bacteria. (A) Open complex formationinvolves the formation of the RNA polymerase holoenzyme, and the recognition of promoter elementsby the !-factor component of the holoenzyme. In this figure, only the !-factor is shown for clarity. TheUP element, where the #-CTD of the RNA polymerase binds is a flexible region of the DNA. (B) Opencomplex formation involves unwinding of the DNA around -10 position relative to transcription startsite. (C) During elongation, the !-factor leaves the holoenzyme (with a few exceptions). The $-subunit, whose role in transcription is obscure is not shown. The DNA double helix is represented as athick grey line; bubbles stand for unwound regions. Adapted from Ussery et al. Springer 2009.DNA; (3) !-factors; (4) TFs; and (5) small-molecule regulators of RNAP activity. The firstthree factors are the most global regulators of transcription, whereas the effects of TFs areconsidered to be more specific to individual promoters. Direct control of RNAP function bysmall molecules such as ppGpp is beyond the scope of this chapter.I.2.2. Promoter sequenceThe canonical bacterial promoter, deduced from studies of E. coli transcription, has twosequence elements that are called the -10 (consensus: TATAAT) and the -35 sites (consensus:TTGACA) positioned 10 and 35 bases upstream of the transcription start site respectively.Two other important elements are the extended -10 region, which is a sequence of 3-4 baseslocated upstream of the -10 site, and the UP element, a ~20bp stretch upstream of the -355
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Chapter 2: Transcriptional control
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Chapter 3: Transcriptional and post
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Chapter 4: Comparative genomics of
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two-domain architectures wherethese
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(A)60% of genomes from class4530150
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Discussion and conclusionsDiscussio
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Discussion and conclusionsD1.1.3. C
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Discussion and conclusionsD2. Futur
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BibliographyAmikam, D., Steinberger
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BibliographyBlattner, F.R., Plunket
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BibliographyChen, S.L., Hung, C.S.,
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BibliographyEchols, N., Harrison, P
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Bibliographysystem level analysis o
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BibliographyHerring, C.D., Raghunat
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BibliographyJenal, U., and Malone,
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BibliographyKeseler, I.M., Collado-
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BibliographyLee, S.H., Angelichio,
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BibliographyMcClelland, M., Sanders
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BibliographyO Croinin, T., Carroll,
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BibliographyPrice, M.N., Dehal, P.S
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BibliographySatriano, J., and Schlo
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BibliographySteinberger, O., Lapido
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BibliographyUssery, D.W., Wassenaar
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BibliographyYanofsky, C. 1981. Atte
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Appendix 1Appendix 1.1: Differences
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Appendix 1Appendix 1.5: Gene expres
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Appendix 2Appendix 2.1: Differences
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Appendix 2Appendix 2.3: Co-regulati
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Appendix 2Appendix 2.5: Flux coupli
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Appendix 2Appendix 2.7: Co-regulati
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Appendix 2Appendix 2.8B: Connectivi
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Appendix 2Appendix 2.10: Correlatio
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Appendix 2Appendix 2.12A: Robustnes
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Appendix 3Appendix 3Supplementary m
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Reaction ID Regulatory metabolite I
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Appendix 3Appendix 3.3B: Direct reg
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Appendix 3Appendix 3.4B: Direct reg
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Appendix 4Appendix 4Supplementary m
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Appendix 4Motile organisms are rich
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Appendix 4We can expand the analysi
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Appendix 5Appendix 5.1A: PFAMs for
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Appendix 5Appendix 5.1C: PFAMs for
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Appendix 5Appendix 5.2B: Small-mole
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Appendix 5Appendix 5.3: Organisms s
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Appendix 5Appendix 5.5: Partner dom
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Appendix 5fraction of SDRRs would a
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Appendix 5Appendix 5.6C: Non-hybrid
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Appendix 5Appendix 5.8: List of org
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Appendix 6Appendix 6List of genomes
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Appendix 648. Mycobacterium tubercu
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Appendix 6144. Bacillus cereus ATCC
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Appendix 6240. Nitrobacter winograd
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Appendix 6336. Cytophaga hutchinson
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Appendix 6432. Acinetobacter bauman
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Appendix 6528. Enterobacter sakazak
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Appendix 6624. Polynucleobacter nec
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Appendix 7Appendix 7List of genomes
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Appendix 748. Bordetella parapertus
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Appendix 7144. Haemophilus somnus14
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Appendix 7240. Prochlorococcus mari
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Appendix 7336. Synechococcus sp. CC
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Downloaded from genome.cshlp.org on
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JOURNAL OF BACTERIOLOGY, June 2008,
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VOL. 190, 2008 P. MIRABILIS GENOME
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2 Nucleic Acids Research, 2008PCR a
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4 Nucleic Acids Research, 2008Table
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6 Nucleic Acids Research, 2008Table
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8 Nucleic Acids Research, 2008solve
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An Assessment of the Role of DNA Ad
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DAM and Transcriptionpotential of s
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