Outside of their homeodomains, HOX protein have no sequence similarities except for two short peptides: 'MXSYF', at their N-termini, and the hexapeptide (also called the 'YPWM' motif or pentapeptide) N-terminal to their homeodomains. A 20 bp human Hoxb-1 promoter oligonucleotide is sufficient to direct an expression pattern in the fly that is very similar to the endogenous labial pattern. This expression pattern requires lab and extradenticle. Labial proteins with mutations in the hexapeptide bind DNA in the absence of EXD and have an increased ability to activate transription in vivo. Proteolysis experiments suggest that EXD can induce a conformational change in LAB. Apparently, LAB hexapeptide inhibits LAB function by inhibiting DNA binding, and an EXD-induced conformational change in LAB relieves this inhibition, promoting highly specific interactions with biologically relevant binding sites (Chan, 1996b).
In the absence of the eight genes of the homeotic cluster (HOM-C), which specify the identity of head, thoracic and abdominal segments, thoracic and abdominal structures develop a 'ground' pattern which includes cephalic structures called sclerotic plates. These plates are specified by empty spiracles. EMS has the potential to induce sclerotic plates, but this potential is suppressed by the HOM-C genes, including the labial gene, the most anteriorly expressed homeotic gene.
When labial is expressed without the other HOM-C genes a stereotyped arch-shaped cephalic structure forms in every thoracic and abdominal segment. This head piece probably represents the contribution of the lab gene to head development. The suppression of the head piece by all other HOM-C genes is the basis of the argument that labial is hierarchically the lowest ranking homeotic gene.
The suppression phenomenon which does not occur at the transcriptional or translational level is called phenotypic suppression. The phenomenon is used to explain posterior dominance, the observation that a homeotic gene product will have an effect only in the body region anterior to the normal domain of the gene. Posterior dominance is given an evolutionary context by the argument that the primordial segment pattern is thoracic-like and that head structures are formed by modifying an archetypal thoracic-like pattern (Macías, 1996).
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