Cis-regulatory logic in archaeal transcription - CiteSeerX

326

Biochemical Society Transactions (2013) Volume 41, part 1

Cis-regulatory logic in archaeal transcription Eveline Peeters*1 , Nuno Peixeiro† and Guennadi Sezonov‡§ *Research group of Microbiology, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium, †Commissariat a` l’Energie Atomique et aux Energies Alternatives (CEA), iBiTec-S, Service de Biologie Integrative ´ et Gen ´ etique ´ Moleculaire, ´ F-91191 Gif-sur-Yvette Cedex, France, ‡Unite´ de Biologie Moleculaire ´ du Gene ` chez les Extremophiles, ˆ Institut Pasteur, 25–28 rue du Dr Roux, F-75724 Paris Cedex 15, France, and §Universite´ Pierre et Marie Curie, UMR 7138 ‘Systematique, ´ Adaptation, Evolution’, Paris, France

Abstract For cellular fitness and survival, gene expression levels need to be regulated in response to a wealth of cellular and environmental signals. TFs (transcription factors) execute a large part of this regulation by interacting with the basal transcription machinery at promoter regions. Archaea are characterized by a simplified eukaryote-like basal transcription machinery and bacteria-type TFs, which convert sequence information into a gene expression output according to cis-regulatory rules. In the present review, we discuss the current state of knowledge about these rules in archaeal systems, ranging from DNA-binding specificities and operator architecture to regulatory mechanisms.

Introduction Micro-organisms respond efficiently to ever-continuing changing environmental conditions by a combination of transcriptional, translational and metabolic regulation. At the level of gene transcription, the largest part of regulation is carried out during the transcription initiation phase by the action of specific TFs (transcription factors). In prokaryotes, specific TFs are mostly single-component systems, i.e. proteins that contain both the DNA-binding domain and the stimulus-response domain and convey stimuli directly into an adapted gene expression response. Stimuli range from smallmolecule ligands that interact with the TF, either metabolites or environmental compounds taken up by the cell, to signals such as light, temperature and the cellular redox state. Archaea are characterized by a eukaryote-type basal transcription machinery, in terms of both structure and organization, although being a simplified version [1–3] (Figure 1A). A basal archaeal promoter is composed of a TATA box, centred at position − 26/ − 27 with respect to the TSS (transcription start site), and a purine-rich BRE (factor B recognition element) located immediately upstream of the TATA box [4]. The unique archaeal RNAP (RNA polymerase) contains up to 13 subunits and shows large structural similarities to the eukaryotic RNAPII, exemplified by the conservation of a characteristic protruding stalk [5,6]. Whereas bacterial RNAP initiates transcription without the involvement of additional factors, archaeal RNAP requires

Key words: activation, Archaea, DNA binding, operator, repression, transcription regulation. Abbreviations used: BRE, factor B recognition element; ChIP, chromatin immunoprecipitation; ChIP-seq, ChIP followed by deep sequencing; HTH, helix–turn–helix; PIC, pre-initiation complex; RHH, ribbon–helix–helix; RNAP, RNA polymerase; SELEX, systematic evolution of ligands by exponential enrichment; TBP, TATA-box-binding protein; TF, transcription factor; TFB, transcription factor B; TSS, transcription start site. 1 To whom correspondence should be addressed (email [email protected]).

C The

C 2013 Biochemical Society Authors Journal compilation

a minimal set of two general TFs: TBP (TATA-box-binding protein) and TFB (transcription factor B). PIC (pre-initiation complex) formation consists of the following steps: first, TBP binds the promoter region at the TATA box. Subsequently, TFB binds the TBP–DNA complex and by recognizing the BRE sequence it determines the correct orientation of the PIC [7]. Finally, RNAP is recruited to the complex and positioned correctly to initiate transcription at the TSS. Several archaeal species contain multiple, divergent tfb and tbp genes and it is hypothesized that these have a regulatory role at a higher level, reminiscent of alternative σ factors in bacteria [8]. Despite having a eukaryote-like basal transcription machinery, archaeal genomic organizational properties such as coding density and operonic structure are bacterialike [9]. Furthermore, specific TFs in archaea, which are mostly single-component TFs, are homologous with bacterial TFs. Approximately 53 % of all identified TFs in archaeal genomes has at least one homologue in bacteria, as opposed to 2 % having a eukaryotic homologue [10]. By far the largest fraction of bacterial/archaeal TFs contain an HTH (helix–turn–helix) motif, followed by the RHH (ribbon– helix–helix) motif (Arc/MetJ domain) and the zinc ribbon [11,12]. Remarkably, TFs with the RHH motif are the most common regulators encoded by hyperthermophilic archaeal viruses [13]. Bacteria-like TFs in archaea and bacteria are postulated to have a common evolutionary origin: before divergence of the bacterial lineage, the last common ancestor of the prokaryotes possessed TFs with motifs similar to the contemporaneous archaeal/bacterial TFs [12]. TFs convert one or more input signals at a specific promoter into a regulatory output. Structural determinants are the TFbinding motifs encoded in the promoter DNA sequence. The present mini-review focuses on mechanisms that determine the control logic relationship between operator architecture and regulatory output in archaeal cells and their viruses. Special interest lies in the intriguing combination of a Biochem. Soc. Trans. (2013) 41, 326–331; doi:10.1042/BST20120312

Molecular Biology of Archaea 3

Figure 1 Main features of archaeal TF binding and mechanisms of regulation (A) Overview of molecular mechanisms of archaeal transcription regulation and binding locations for which the corresponding mechanism has been observed, ranging from far upstream of promoter (A), close upstream of promoter (B), overlapping core promoter (C), downstream of promoter (D) to downstream of TSS (E). The symbol + indicates that the mechanism has been demonstrated, the symbol ( + ) indicates that the mechanism has been postulated without conclusive proof. (B) Selected examples of DNA-binding specificities of archaeal TFs: Phr of P. furiosus [22], Ss-LrpB of S. solfataricus [20,35] and the as yet unidentified TF regulating arabinose metabolic and transport genes in Sulfolobus sp. [31]. Specificities are based on identified binding sites, and represented as sequence logos, which are ordered stacks of letters in which each letter’s height indicates the information content at a particular position of the binding motif. Sequence logos have been constructed with WebLogo [50] (http://www.weblogo.berkeley.edu).

eukaryote-type basal transcription machinery and bacterialike TFs.

Architecture of archaeal operators The molecular basis of the functioning of a TF is founded in its sequence-specific interaction with the DNA. Detailed studies of the DNA-binding sequence specificity (determined by the relative binding affinities to all possible binding sites) of archaeal TFs are relatively scarce. Often, only a limited number of binding sites is known on the basis of experimental or in silico (e.g. phylogenetic footprinting) approaches. Mutational analysis of binding sites, combined with in vitro DNA-binding assays [14–24], in vitro transcription assays [25] or in vivo reporter gene assays [21,26,27], have provided deeper insights into the DNA-binding energy landscape and corresponding regulatory outputs for a variety of archaeal TFs. For some of these proteins, a higher-resolution DNAbinding profile has been obtained by applying the method of SELEX (systematic evolution of ligands by exponential enrichment) [24,28,29]. ChIP-on-chip [ChIP (chromatin immunoprecipitation) using microarrays] or ChIP-seq (ChIP followed by deep sequencing), which are among the most powerful techniques to map DNA-binding sites of a TF genome-wide in an in vivo context, has been rarely applied in archaea [30], despite its proven success in bacterial and eukaryotic systems.

Given the bacterial nature of DNA-binding motifs, it is evident that archaeal TFs recognize specific DNA sequences in a similar fashion as their bacterial counterparts. DNA sequence motifs have almost invariably a semi-palindromic nature, which reflects the two-fold symmetry of the binding proteins caused by homodimerization. Examples of DNAbinding sequence specificities for a selection of archaeal TFs are shown in Figure 1(B). Sizes of binding motifs can range from a minimal 8 bp, exemplified by the ARA box motif in Sulfolobus [27,31] to 24 bp, as is the case for the heat-shock regulator Phr in Pyrococcus furiosus [22]. Typical binding motifs usually have a size between 11 and 17 bp with a number of less- or non-informative base pairs in the centre. Each dyad symmetry-determining half-site allows base-specific interactions in the major groove of the DNA, either with the recognition α-helix of an HTH motif [12] or with the β-sheet face of a RHH motif [32]. The alignment of two half-sites in a binding site is highly constrained, as demonstrated for SsLrpB from Sulfolobus solfataricus: whereas an insertion of 1 or 2 bp in the centre of the binding site is still tolerated, albeit resulting in a much lower binding affinity, a 1 bp deletion completely abolishes DNA binding, pointing to a limited conformational flexibility of the TF protein [17]. Binding to a single site is exceptional; most TFs recognize an array of binding sites, resulting in homoco-operative binding, which enhances the global binding affinity, but also leads to a higher sensitivity and a non-linear regulatory response. Frequently, there is one primary site that exerts C The


327

328


regulation, whereas the other sites are auxiliary operators merely assisting in the occupation of the primary site and contributing to repression or activation only to a minor extent. For example, besides the ARA box located close to the araS promoter in Sulfolobus, a distal upstream ARA box was identified that can be deleted without affecting activation [27]. For Ptr2 from Methanocaldococcus jannaschii, an auxiliary site was identified inside the ORF (open reading frame) that is bound but does not contribute to activation [25]. There are spatial constraints on the placement of multiple binding sites and these are usually governed by the DNA helical structure in such a way that it allows binding of different TF molecules to the same face of the helix. Centre-to-centre distances corresponding to two or three full helical turns between juxtaposed binding sites are most common [20,21,25,33–36]. Decreasing or increasing this spacing with a half-helical turn (5–6 bp) affects DNA-binding co-operativity, affinity and the resulting regulatory effect ([25,36] and E. Peeters and D. Charlier, unpublished work). Binding sites are not always as well delineated as in the above examples: in some cases, initial binding to a core binding site causes extensive co-operative binding extending in one direction from the nucleation site [18,20,24]. In this additionally bound region, only highly degenerated binding motifs can be recognized.

Molecular mechanisms of transcription regulation The relative positions of TF-binding sites with respect to the promoter and TSS are also constrained. Whether a TF acts as an activator or as a repressor does not depend on a specific DNA-binding mechanism or protein domain, but is usually determined by the binding site location with respect to the promoter (Figure 1A). Although it is difficult to unambiguously predict regulatory effects based merely on these locations, it is clear that activators have a tendency to bind upstream of the promoter and repressors overlapping with or downstream of the promoter.

Repressors Two major repression mechanisms have been described in archaea and archaeoviruses. A first mechanism entails the binding of the TF at a site overlapping the BRE and TATA box promoter elements thereby impairing promoter access for TBP and TFB through steric hindrance [16,19,22,23,37,38]. In a second mechanism, the TF binds to a site downstream of the TATA box. In this case, the binding of TBP and TFB is not prevented, but instead the recruitment of RNAP is inhibited [21,23,33,38–41]. Such a mechanism is employed by the hetero-oligomeric NrpRI–NrpRII repressor complex ¨ and it has in the methanogen Methanosarcina mazei Go1, been demonstrated that this repressor complex establishes protein–protein interactions with TBP and TFB thereby sequestering the basal TFs at the promoter [41]. It is speculated that both repression mechanisms invoke a different responsiveness upon derepression: whereas in the case of TBP/TFB inhibition, the entire PIC needs to C The


be formed before transcription can be initiated, the second mechanism allows the pre-bound TBP and TFB to rapidly recruit RNAP after derepression leading to a shorter response time [37]. Depending on the biological function of the target gene(s) and associated input signals, this responsiveness could be crucial for cellular fitness. Curiously, the tryptophanresponsive TrpY of Methanothermobacter thermautotrophicus implements both mechanisms simultaneously by binding the intergenic region of a divergent operon and regulating one arm (trpY-autoregulation) by blocking RNAP recruitment and the other arm (trpEGCFBAD) by inhibiting TBP binding [18]. Not all repression mechanisms observed in archaeal systems can be classified under these two major repression mechanisms: occurrences have been reported of repressors that initially bind only upstream of the core promoter, but displace TBP and TFB by extending this binding further downstream, as has been shown for the RHH-containing AvtR from an archaeal lipothrixvirus [24] and for TrpY [18]. In the latter case, the protein constrains negative supercoils into the DNA.

Activators Characterized transcriptional activators usually bind at a single or primary operator site located immediately upstream or partially overlapping BRE [20,25–27,34,42], which is also called the upstream activating sequence. For traditional 15– 17 bp sites, this binding location positions the TF at the same helical face as the basal TFs (centre-to-centre distance of approximately two helical turns between TF-binding site and TATA box). In the case of Ptr2, it has been demonstrated that this spacing is critical for activation [25]. Auxiliary operator sites are located upstream of the primary site, downstream of the TATA box (as shown for Sta1 [43]), or downstream of the TSS [25]. Exceptions have been described in which TFs activate a promoter from a nucleation site located further upstream with binding progressing towards the promoter at higher concentrations [20,24]. For those activators for which the mechanistic details have been unravelled, it is clear that activation occurs at one of the initial steps of PIC assembly, namely binding of TBP or TFB by means of stimulating protein–protein interactions. In contrast with repressors, which can function in combination with any promoter strength, activators are generally associated with promoters having large deviations from the consensus BRE and/or TATA box sequences [34,42,44]. Furthermore, the activation effect can only be observed in vitro in the presence of minimal concentrations of the basal TFs. Whereas for some activators, specific interactions with either TBP [34] or TFB [42,44] have been demonstrated, other activators such as the gas vesicle regulator GvpE are able to interact with both [45,46]. Moreover, GvpE interacts with five different TBPs of Halobacterium salinarum [45].

Dual regulators Not all TFs in archaea have a dedicated function as either activator or repressor. For example, TrmBL1, Tgr, SurR and


Figure 2 Autoregulation by the S. solfataricus TF Ss-LrpB (A) Autoradiograph of an in vitro transcription assay with a negatively supercoiled plasmid containing the Ss-lrpB promoter as template. In vitro transcription with Sulfolobus TFs and RNAP was performed as described previously [32]. Each transcription reaction was performed with 100 ng of plasmid DNA, 200 ng of TBP, 200 ng of TFB and 500 ng of RNAP. Synthesized RNA was detected by means of primer extension with a sequence-specific gel-purified 32 P-labelled primer. The RM (recovery marker) is a labelled fragment that was added to the transcription reaction mixtures before extraction and precipitation. Ss-LrpB concentrations are indicated on top of the lanes in nM. The ‘switch’ between activation and repression has been observed repeatedly, with the level of activation being dependent on the transcription conditions (concentrations of active TBP, TFB, RNAP and Ss-LrpB). Below the autoradiograph, a quantification plot is shown. The relative amount of transcripts, normalized against the RM signal and against the transcription level in the reaction without Ss-LrpB (= 1.0), is given as a function of the Ss-LrpB concentration. (B) A hypothetical model of the autoregulatory process of Ss-LrpB. Binding sites of Ss-LrpB (Box1, Box2 and Box3) and the main promoter elements BRE, TATA box and initiator (Inr), containing the first transcribed nucleotide, are indicated (HA, high affinity; LA, low affinity). The scheme displays the major Ss-LrpB-DNA-binding states that exist in a dynamic equilibrium, and the assumed regulatory output (activation or repression) for each of these binding states.

AvtR can perform either function at different promoters depending on the position of the binding site [19,38,40]. We have gathered proof that the HTH-containing TF Ss-LrpB from S. solfataricus can bring on opposite regulatory effects at the same promoter, namely the promoter of its own gene, in a concentration-dependent manner (Figure 2). Ss-LrpB binds three distinct regularly spaced binding sites, coined Box1, Box2 and Box3, immediately upstream of the promoter [35]. The two outer boxes, Box1 and Box3, are high-affinity boxes, whereas the middle box, Box2, exhibits very low binding affinity. Box2 is only stably contacted when both outer boxes are already occupied [35]. Imaging by AFM (atomic force microscopy) showed the formation of a highly dense complexed region in which the DNA appears to be wrapped [47]. The assembly of the Ss-LrpB–operator autoregulatory complex is a complicated process involving the formation of several different binding states and significant conformational changes in the DNA. However, the nature of the resulting

regulatory effects (autorepression and/or autoactivation) is so far unknown. To analyse the effect of Ss-LrpB on gene expression, we conducted an in vitro transcription assay with a reconstituted Sulfolobus transcription system (Figure 2A). Using a supercoiled DNA template containing the Ss-lrpB operator region, we observed a dual regulatory effect of SsLrpB as a function of the protein concentration. At 13 nM Ss-LrpB, the level of transcription increased significantly with respect to the basal level. At a concentration only 4.5-fold higher, Ss-LrpB affected transcription clearly in a negative instead of positive manner. Thus Ss-LrpB autoregulation appears to be a highly sensitive concentration-dependent switch between autoactivation and autorepression. Further experimental work is required to reveal the underlying mechanisms of this complex regulatory response, but it can be envisaged that different binding states exhibit different regulatory outcomes and that Ss-LrpB-induced changes C The


329

330


in the local DNA topology, caused by the wrapping, in the saturated complex might contribute to the observed repression (Figure 2B).

Concluding remarks Archaeal TFs interact with DNA in a bacteria-like mode, in terms of both binding motif sequences and relative locations with respect to the promoter (i.e. close to or overlapping with the core promoter). However, the mechanisms of the modulation of transcription initiation efficiency are fundamentally different from bacterial TFs given the different nature of the basal transcription machinery. Whereas repressors can inhibit the binding of any of the elements of the PIC, activators interact with TBP and/or TFB. Main tendencies emerge, but despite significant efforts to understand cis-regulatory logic of archaeal TFs, only a minor subset of all existing archaeal TFs have been characterized so far. Therefore it will not be surprising if future investigations unravel a wider variation of regulatory strategies and mechanisms, which might be more complicated than initially thought (as exemplified by Ss-LrpB autoregulation). Furthermore, as in bacterial and eukaryotic organisms, it is anticipated that transcription regulatory networks exist in archaea, which are not yet well understood. In the future, state-of-the-art high-throughput techniques, such as ChIP-seq, SELEX-seq, protein-binding microarrays, microfluidics measurements of protein–DNA interactions and high-throughput gene reporter measurements [48,49], could assist in accelerating the gain in knowledge of DNAbinding specificities of archaeal TFs and the associated cisregulatory rules that determine gene expression output.

Acknowledgements We thank Daniel Charlier for a critical reading of the paper. E.P. is a postdoctoral fellow of the Research Foundation Flanders (Fonds voor Wetenschappelijk Onderzoek – Vlaanderen).

References 1 Geiduschek, E.P. and Ouhammouch, M. (2005) Archaeal transcription and its regulators. Mol. Microbiol. 56, 1397–1407 2 Grohmann, D. and Werner, F. (2011) Recent advances in the understanding of archaeal transcription. Curr. Opin. Microbiol. 14, 318–324 3 Bell, S.D. (2005) Archaeal transcriptional regulation: variation on a bacterial theme? Trends Microbiol. 13, 262–265 4 Soppa, J. (1999) Normalized nucleotide frequencies allow the definition of archaeal promoter elements for different archaeal groups and reveal base-specific TFB contacts upstream of the TATA box. Mol. Microbiol. 31, 1589–1592 5 Hirata, A. and Murakami, K.S. (2009) Archaeal RNA polymerase. Curr. Opin. Struct. Biol. 19, 1–8 6 Korkhin, Y., Unligil, U.M., Littlefield, O., Nelson, P.J., Stuart, D.I., Sigler, P.B., Bell, S.D. and Abrescia, N.G.A. (2009) Evolution of complex RNA polymerases: the complete archaeal RNA polymerase structure. PLoS Biol. 7, e102 C The


7 Bell, S.D., Kosa, P.L., Sigler, P.B. and Jackson, S.P. (1999) Orientation of the transcription preinitiation complex in archaea. Proc. Natl. Acad. Sci. U.S.A. 96, 13662–13667 8 Facciotti, M.T., Reiss, D.J., Pan, M., Kaur, A., Vuthoori, M., Bonneau, R., Shannon, P., Srivastava, A., Donohoe, S.M., Hood, L.E. and Baliga, N.S. (2007) General transcription factor specified global gene regulation in archaea. Proc. Natl. Acad. Sci. U.S.A. 104, 4630–4635 9 Koonin, E.V. and Wolf, Y.I. (2008) Genomics of bacteria and archaea: the emerging dynamic view of the prokaryotic world. Nucleic Acids Res. 36, 6688–6719 10 Perez-Rueda, ´ E. and Janga, S.C. (2010) Identification and genomic analysis of transcription factors in archaeal genomes exemplifies their functional architecture and evolutionary origin. Mol. Biol. Evol. 27, 1449–1459 11 Aravind, L. and Koonin, E.V. (1999) DNA-binding proteins and evolution of transcription regulation in the archaea. Nucleic Acids Res. 27, 4658–4670 12 Aravind, L., Anantharaman, V., Balaji, S., Babu, M.M. and Iyer, L.M. (2005) The many faces of the helix–turn–helix domain: transcription regulation and beyond. FEMS Microbiol. Rev. 29, 231–262 13 Prangishvili, D., Garrett, R.A. and Koonin, E.V. (2006) Evolutionary genomics of archaeal viruses: unique viral genomes in the third domain of life. Virus Res. 117, 52–67 14 Vierke, G., Engelmann, A., Hebbeln, C. and Thomm, M. (2003) A novel archaeal transcriptional regulator of heat shock response. J. Biol. Chem. 278, 18–26 15 Xie, Y. and Reeve, J.N. (2005) Regulation of tryptophan operon expression in the archaeon Methanothermobacter thermautotrophicus. J. Bacteriol. 187, 6419–6429 16 Lee, S.J., Moulakakis, C., Koning, S.M., Hausner, W., Thomm, M. and Boos, W. (2005) TrmB, a sugar sensing regulator of ABC transporter genes in Pyrococcus furiosus exhibits dual promoter specificity and is controlled by different inducers. Mol. Microbiol. 57, 1797–1807 17 Peeters, E., Wartel, C., Maes, D. and Charlier, D. (2007) Analysis of the DNA-binding sequence specificity of the archaeal transcriptional regulator Ss-LrpB from Sulfolobus solfataricus by systematic mutagenesis and high resolution contact probing. Nucleic Acids Res. 35, 623–633 18 Karr, E.A., Sandman, K., Lurz, R. and Reeve, J.N. (2008) TrpY regulation of trpB2 transcription in Methanothermobacter thermautotrophicus. J. Bacteriol. 190, 2637–2641 19 Lipscomb, G.L., Keese, A.M., Cowart, D.M., Schut, G.J., Thomm, M., Adams, M.W.W. and Scott, R.A. (2009) SurR: a transcriptional activator and repressor controlling hydrogen and elemental sulphur metabolism in Pyrococcus furiosus. Mol. Microbiol. 71, 332–349 20 Peeters, E., Albers, S.-V., Vassart, A., Driessen, A.J.M. and Charlier, D. (2009) Ss-LrpB, a transcriptional regulator from Sulfolobus solfataricus, regulates a gene cluster with a pyruvate ferredoxin oxidoreductaseencoding operon and permease genes. Mol. Microbiol. 71, 972–988 21 Lie, T.J., Hendrickson, E.L., Niess, U.M., Moore, B.C., Haydock, A.K. and Leigh, J.A. (2010) Overlapping repressor binding sites regulate expression of the Methanococcus maripaludis glnK 1 operon. Mol. Microbiol. 75, 755–762 22 Keese, A.M., Schut, G.J., Ouhammouch, M., Adams, M.W.W. and Thomm, M. (2010) Genome-wide identification of targets for the archaeal heat shock regulator Phr by cell-free transcription of genomic DNA. J. Bacteriol. 192, 1292–1298 23 Karr, E.A. (2010) The methanogen-specific transcription factor MsvR regulates the fpaA-rlp-rub oxidative stress operon adjacent to msvR in Methanothermobacter thermautotrophicus. J. Bacteriol. 192, 5914–5922 24 Peixeiro, N., Keller, J., Collinet, B., Leulliot, N., Campanacci, V., Cortez, D., Cambillau, C., Nitta, K.R., Vincentelli, R., Forterre, P. et al. (2013) Structure and function of AvtR, a novel transcriptional regulator from a hyperthermophilic archaeal lipothrixvirus. J. Virol. 87, 124–136 25 Ouhammouch, M., Langham, G.E., Hausner, W., Simpson, A.J., El-Sayed, N.M.A. and Geiduschek, E.P. (2005) Promoter architecture and response to a positive regulator of archaeal transcription. Mol. Microbiol. 56, 625–637 26 Bauer, M., Marschaus, L., Reuff, M., Besche, V., Sartorius-Neef, S. and Pfeifer, F. (2008) Overlapping activator sequences determined for two oppositely oriented promoters in halophilic archaea. Nucleic Acids Res. 36, 598–606 27 Peng, N., Xia, Q., Chen, Z., Liang, Y.X. and She, Q. (2009) An upstream activation element exerting differential transcriptional activation on an archaeal promoter. Mol. Microbiol. 74, 928–939


28 Ouhammouch, M. and Geiduschek, E.P. (2001) A thermostable platform for transcriptional regulation: the DNA-binding properties of two Lrp homologs from the hyperthermophilic archaeon Methanococcus jannaschii. EMBO J. 20, 146–156 29 Yokoyama, K., Nogami, H., Kabasawa, M., Ebihara, S., Shimowasa, A., Hashimoto, K., Kawashima, T., Ishijama, S.A. and Suzuki, M. (2009) The DNA-recognition mode shared by archaeal feast/famine-regulatory proteins revealed by the DNA-binding specificities of TvFL3, FL10, FL11 and Ss-LrpB. Nucleic Acids Res. 37, 4407–4419 30 Schmid, A.K., Reiss, D.J., Pan, M., Koide, T. and Baliga, N.S. (2009) A single transcription factor regulates evolutionarily diverse but functionally linked metabolic pathways in response to nutrient availability. Mol. Syst. Biol. 5, 282 31 Brouns, S.J.J., Walther, J., Snijders, A.P.L., van de Werken, H.J.G., Willemen, H.L.D.M., Worm, P., de Vos, M.G., Andersson, A., Lundgren, M., Mazon, H.F. et al. (2006) Identification of the missing links in prokaryotic pentose oxidation pathways: evidence for enzyme recruitment. J. Biol. Chem. 281, 27378–27388 32 Guilliere, ` F., Peixeiro, N., Kessler, A., Raynal, B., Desnoues, N., Keller, J., Delepierre, M., Prangishvili, D., Sezonov, G. and Guijarro, J.I. (2009) Structure, function, and targets of the transcriptional regulator SvtR from the hyperthermophilic archaeal virus SIRV1. J. Biol. Chem. 284, 22222–22237 33 Bell, S.D., Cairns, S.S., Robson, R.L. and Jackson, S.P. (1999) Transcriptional regulation of an archaeal operon in vivo and in vitro. Mol. Cell 4, 971–982 34 Ouhammouch, M., Dewhurst, R.E., Hausner, W., Thomm, M. and Geiduschek, E.P. (2003) Activation of archaeal transcription by recruitment of the TATA-binding protein. Proc. Natl. Acad. Sci. U.S.A. 100, 5097–5102 35 Peeters, E., Thia-Toong, T.-L., Gigot, D., Maes, D. and Charlier, D. (2004) Ss-LrpB, a novel Lrp-like regulator of Sulfolobus solfataricus P2, binds cooperatively to three conserved targets in its own control region. Mol. Microbiol. 54, 321–336 36 Lie, T.J., Wood, G.E. and Leigh, J.A. (2005) Regulation of nif expression in Methanococcus maripaludis: roles of the euryarchaeal repressor NrpR, 2-oxoglutarate, and two operators. J. Biol. Chem. 280, 5236–5241 37 Bell, S.D. and Jackson, S.P. (2000) Mechanism of autoregulation by an archaeal transcriptional repressor. J. Biol. Chem. 275, 31624–31629 38 Lee, S.-J., Surma, M., Hausner, W., Thomm, M. and Boos, W. (2008) The role of TrmB and TrmB-like transcriptional regulators for sugar transport and metabolism in the hyperthermophilic archaeon Pyrococcus furiosus. Arch. Microbiol. 190, 247–256

39 Dahlke, I. and Thomm, M. (2002) Pyrococcus homolog of the leucine-responsive regulatory protein, LrpA, inhibits transcription by abrogating RNA polymerase recruitment. Nucleic Acids Res. 30, 701–710 40 Kanai, T., Akerboom, J., Takedomi, S., van de Werken, H.J.G., Blombach, F., van der Oost, J., Murakami, T., Atomi, H. and Imanaka, T. (2007) A global transcriptional regulator in Thermococcus kodakaraensis controls the expression levels of both glycolytic and gluconeogenic enzyme-encoding genes. J. Biol. Chem. 282, 33659–33670 41 Weidenbach, K., Ehlers, C., Kock, J. and Schmitz, R.A. (2010) NrpRII mediates contacts between NrpRI and general transcription factors in the archaeon Methanosarcina mazei Go1. ¨ FEBS J. 277, 4398–4411 42 Ochs, S.M., Thumann, S., Richau, R., Weirauch, M.T., Lowe, T.M., Thomm, M. and Hausner, W. (2012) Activation of archaeal transcription mediated by recruitment of transcription factor B. J. Biol. Chem. 287, 18863–18871 43 Kessler, A., Sezonov, G., Guijarro, J.I., Desnoues, N., Rose, T., Delepierre, M., Bell, S.D. and Prangishvili, D. (2006) A novel archaeal regulatory protein, Sta1, activates transcription from viral promoters. Nucleic Acids Res. 34, 4837–4845 44 Peng, N., Ao, X., Liang, Y.X. and She, Q. (2011) Archaeal promoter architecture and mechanism of gene activation. Biochem. Soc. Trans. 39, 99–103 45 Teufel, K. and Pfeifer, F. (2010) Interaction of transcription activator GvpE with TATA-box-binding proteins of Halobacterium salinarum. Arch. Microbiol. 192, 143–149 46 Bleiholder, A., Frommherz, R., Teufel, K. and Pfeifer, F. (2011) Expression of multiple tfb genes in different Halobacterium salinarum strains and interaction of TFB with transcriptional activator GvpE. Arch. Microbiol. 194, 269–279 47 Peeters, E., Willaert, R., Maes, D. and Charlier, D. (2006) Ss-LrpB from Sulfolobus solfataricus condenses about 100 base pairs of its own operator DNA into globular nucleoprotein complexes. J. Biol. Chem. 281, 11721–11728 48 Stormo, G.D. and Zhao, Y. (2010) Determining the specificity of protein–DNA interactions. Nat. Rev. Genet. 11, 751–760 49 Sharon, E., Kalma, Y., Sharp, A., Raveh-Sadka, T., Levo, M., Zeevi, D., Keren, L., Yakhini, Z., Weinberger, A. and Segal, A. (2012) Inferring gene regulatory logic from high-throughput measurements of thousands of systematically designed promoters. Nat. Biotechnol. 30, 521–530 50 Crooks, G.E., Hon, G., Chandonia, J.M. and Brenner, S.E. (2004) WebLogo: a sequence logo generator. Genome Res. 14, 1188–1190 Received 1 November 2012 doi:10.1042/BST20120312

C The


331