The Expression Pattern of the Murine Hoxa-10 Gene and the Sequence Recognition of Its Homeodomain Reveal Specific Properties of Abdominal B-like Genes

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Abstract
Homeobox genes of the Abdominal B (AbdB) family constitute a distinct subset of vertebrate Hox genes. Analysis of the murine Hoxa-10 gene, one member of this family, revealed several properties specific to this class. Two transcripts of Hoxa-10, a10-1 and a10-2, encode homeodomain proteins of 55 kDa (399 amino acids) and 16 kDa (96 amino acids), respectively. These proteins have identical homeodomains and C-terminal regions encoded by a common 3' exon but differ significantly in the sizes of their N-terminal regions because of the usage of alternative 5' exons. The 5' exon of the a10-2 form is also present in transcripts of Hoxa-9, the next 3' gene, indicating that splicing can occur between adjacent AbdB Hox genes within a cluster. Both Hoxa-10 transcripts demonstrated identical patterns of expression in the posterior body and proximal limb bud, differentiating them from AbdB morphogenetic and regulatory transcripts and suggesting a role with other AbdB Hox genes in the patterning of these structures. Finally, a binding site selection identified the sequence AA(A/T)TTTTATTAC as the Hoxa-10 homeodomain consensus binding site, with a TTAT core sequence. Preferential recognition of a TTAT core therefore differentiates the AbdB class from Antennapedia (Antp) class gene products which bind a TAAT core. Thus, in vertebrates, structural similarities, coordinate transcriptional regulation, sites of expression, and binding site preferences all serve to distinguish AbdB from Antp Hox genes.