Figure 1.
Networks motifs found in the H. pylori TRN.
A. Single input motif (SIM); a single transcription factor A regulates a set of operons (X, Y, Z); frequently A is autoregulated. B. multicomponent loop (MCL); transcription factor A regulates another regulator B, which in turn can regulate the transcription of A; each regulator can also control transcription of a separate set of target operons. C. Feed forward loops (FFLs) are three node motifs, occurring with high frequency in prokaryotic TRNs. A top regulator, A, which controls a second regulator, B, and a target gene, X, which is regulated by both A and B. The regulators in this motif (A, B) have an asymmetric position and hierarchy, as A regulates two targets, while B only one. According to the net signs feeding into X, FFL can be coherent (same sign) or incoherent (opposite sign), negative or positive, conferring different response kinetics [13] D. Bifan motif (BM); a set of operons (X, Y) is each regulated by the combination of two (A, B; BM) or multiple (A, B, C, etc.; multi input motif, not shown) transcription factors.
Table 1.
H. pylori transcription factors and regulators.
Figure 2.
The heat shock and stress response origon.
A. The heat shock origon is composed of two TFs (HspR and HrcA) repressing directly three main target operons: I) the cbp operon, encoding, respectively, a DnaJ-homologue CbpA, the HspR regulator itself, and a gene product of unknown function with homology to a helicase (HP1026); II) the hrcA operon, coding for the HrcA regulator, DnaK, and the GrpE co-chaperone; and III) the groESL operon, encoding conserved GroES and GroEL chaperones. Block arrows: open reading frames. Green boxes: HrcA operators; blue boxes, HspR operators. −10 and −35 boxes are depicted by black and white squares, respectively. TF–DNA interactions and direct transcriptional control are depicted by black lines; red dotted lines represent protein–protein interactions important for feedback control of the circuit; arrowheads denote positive regulation; hammerheads indicate negative regulation. B. Incoherent type-2 FFL wiring of HspR, HrcA, and the groESL operon, responsible for the prompt derepression kinetics of Pgro upon heat shock. Red line: derepression kinetic of the intact FFL motif; blue dotted line: derepression kinetic of a mutated Pgro promoter in which the HspR operator has been deleted. The membrane association of HrcA in H. pylori [47] may confer additional sensory potential to the circuit, e.g., through sensing of periplasmic misfolded peptides, or need to release HrcA from the inner membrane by a stress-inducible co-factor.
Figure 3.
The flagellar biosynthesis module.
RNAP, RNA polymerase; phosphorylation events are indicated by a light blue circle. CheAY, two component system involved in chemotaxis; FlgS, NtrB-like cytoplasmic histidine kinase; FlgR, NtrC-like response regulator. FlgM, anti-σ28 factor. FlhA, FlhF, HP0958: accessory factors. Note sequential activation of class I, II, and III due to σ regulatory cascade. A pink triangle depicts a putative coherent FFL with OR logic proposed to control expression of intermediate class flagellar genes [32].
Figure 4.
Fur regulates transcription of metal transporters and siderophores (e.g., frpB and fecA paralogues), which need to be repressed upon iron repletion [66]–[68], as well as detoxifying genes that need to be promptly derepressed under the same Fe2+ replete conditions (e.g., pfr bacterioferritin and sod superoxide dismutase) [69], [70]. Fur generally acts as repressor, but it may also act positively on transcription on certain genes (flaB, oor) [74]. Similarly, NikR can act as positive or negative regulator of transcription, according to the position of the operator elements [79], [80]. With respect to the promoter, binding upstream appears to induce transcription of the ureAB operon in cultures grown in Ni2+ replete cultures [64]. Conversely, binding within the core promoter represses transcription, as shown for the fecA3 and frpB4 genes, encoding outer membrane proteins [68], [103], [105], the nixA permease gene [106], and the exbBD-tonB operon, that is involved in energization of outer membrane transport complexes involved in metal uptake [107], and itself part of the Fur regulon [74], [75], [81], [104]. Note that both Fur and NikR are autoregulated, and that they control reciprocally their transcription levels, through direct binding to their respective promoters [81]. Several operons such as exbBD-tonB are under the control of both Fur and NikR.