Multiple target sites

The establishment of the complex temporo-spatial expression pattern of the Hox genes is likely to require cis-regulatory regions containing multiple target sequences for numerous specific transcription factors. There is evidence for multiple spatially specific enhancers that work over a distance and they may influence several genes including Hox-2.6 gene (Whiting et al., 1991). In Hox-3.2 - Hox-3.1 intergenic region there are several potential sequences for interactions with HD and zinc finger proteins. These include two sequences recognized by Hox-1.3 protein, six binding sites for Sp1 transcription factor, six sites resembling Antp-protein recognition site, five sites similar SV40 enhancer, up to six sequence motifs similar to several hormone response elements (including up to four motifs which may mediate response to RA), five copies of heat shock elements, and some other motifs (Structural analysis of the Hox-3.1 transcription unit and the Hox-3.2--Hox-3.1 intergenic region.Awgulewitsch et al., 1990. Differential expression of Hox 3.1 protein in subregions of the embryonic and adult spinal cord.Awgulewitsch et al., 1990). Six GC-rich domains with several Sp1 binding sites has been found in the promoter region of the Hox-1.4 gene (Galliot et al., 1989). The upstream region of the human Hox-3D gene is a target for RA and HD-proteins (Arcioni et al., 1992). Seven distinct protein binding sites with several Sp1 and USF binding sites were found in murine Hox-2.3 promoter (Zwartkruis et al., 1991). There are similarities in structure of this and Hox-1.4 promoter region. Multiple copies of protein recognition sites are thought to act synergistically, presumably due to some functional cooperativity of the regulatory protein involved (Jaynes & O'Farrell, 1988). These cooperativity presumably yield sharp gene activation thresholds (Struhl et al., 1989).