Common History at the Origin of the Position-Function Correlation in Transcriptional Regulators in Archaea and Bacteria

Abstract

Abstract. Regulatory proteins in Escherichia coliwith a helix-turn-helix (HTH) DNA binding motif show a position-function correlation such that repressors have this motif predominantly at the N terminus, whereas activators have the motif at the C-terminus extreme. Using this initial collection we identified by sequence comparison the exhaustive set of transcriptional regulators in 17 bacterial and 6 archaeal genomes. This enlarged set shows the same position-function correlation. The main question we address is whether this correlation is the result of common origin in evolution or the result of convergence. Evidence is presented supporting a common history at the origin of this correlation. We show the existence of a supergroup of eight repressor protein families sharing a conserved extended sequence comprising the classic HTH. Two of these repressor families (MarR and AsnC) originated before the divergence of Archaea and Bacteria. They are proposed at the origin of HTHbearing transcriptional regulators currently present in Bacteria. The group of LysR proteins, with the HTH also at the N terminus, offers a control to the argument, since it shows clearly distinctive structural, functional, and evolutionary properties. This group of activator proteins, suggested to have originated within the Bacteria, has an advantageous gene organization to facilitate its horizontal transfer-used to conquer some Archaea-as well as negative autoregulation convenient for homeostasis, all of which agrees with this being the largest family in Bacteria. These results suggest that if shuffling of motifs occurred in Bacteria, it occurred only early in the history of these proteins, as opposed to what is observed in eukaryotic regulators.

The TetR Family of Transcriptional Repressors

“…One protein is usually a membrane-linked kinase that, upon sensing the appropriate signal, phosphorylates a DNAbinding protein that mediates transcription from its cognate promoter. Structural analyses have revealed that the helixturn-helix (HTH) signature is the most recurrent DNAbinding motif in prokaryotic transcriptional factors, since almost 95% of all transcriptional factors described in prokaryotes use the HTH motif to bind their target DNA sequences (12,19,27,41,43,104,135,136,302,335,343).…”

The TetR Family of Regulators

“…It has been suggested that there is a correlation between the location of the DNA-binding domain and repressor and activator activity. The suggestion was that repressors generally contain an N-terminal DNA-binding domain, while activators generally contain a C-terminal DNA-binding domain (4,5). While this may hold true for many transcription factors, we would advise caution because there are well-documented exceptions to this rule (6).…”

Transcription by Methanothermobacter thermautotrophicus RNA Polymerase In Vitro Releases Archaeal Transcription Factor B but Not TATA-Box Binding Protein from the Template DNA

“…Consistent with the archaeal regulatory systems characterized to date superficially resembling bacterial systems, archaeal and bacterial regulators do appear to have common ancestries (1,16,20). Repressors apparently block, and activators stimulate, transcription initiation by binding to DNA sequences in upstream regions (6,14,21,24).…”

“…For the autorepressor Lrs14 (5), Lrs14 and TBP/ TFB binding to the BRE-TATA-box region upstream of lrs14 have been shown to be mutually exclusive, with added Lrs14 incapable of dislodging prebound TFB/TBP in vitro and vice versa. In the one archaeal transcription activation system reproduced in vitro, the activator binds upstream of the BRE/ TATA box, and this increases the affinity of TBP for the TATA-box sequence (19).Consistent with the archaeal regulatory systems characterized to date superficially resembling bacterial systems, archaeal and bacterial regulators do appear to have common ancestries (1,16,20). Repressors apparently block, and activators stimulate, transcription initiation by binding to DNA sequences in upstream regions (6,14,21,24).…”