Gene structure and transcription regulation of mammalian O-sialoglycoprotein endopeptidase gene

O-sialoglycoprotein endopeptidase (EC 3.4.24.57) is a unique enzyme that specifically cleaves the polypeptide backbone of glycoproteins having O-linked sialoglycans. The glycoprotease (gcp) enzyme purified from Pasteurella haemolytica is the best characterized. Orthologs of the gcp enzyme have been found to be conserved throughout all organisms with fully sequenced genomes. The gene for the mammalian homolog (OSGEP1/Osgep1) consists of 11 exons and 10 introns, and lies immediately adjacent to the gene for APEX nuclease (APEX/Apex), a DNA repair enzyme, in a head-to-head orientation. The gene is found on human chromosome 14q11.2-q12 and on mouse chromosome 14C2-D1. The head-to-head orientation and very close proximity of OSGEP1/Osgep1 and APEX/Apex genes imply that overlapping promoters drive transcription of both genes. These genes are believed to be housekeeping genes because they possess properties such as ubiquitous expression, putative promoters in a CpG island, multiple transcription initiation sites, and the absence of a typical TATA box. The functional elements of the transcriptional core promoter of the mouse Osgep1 and Apex genes have been identified by luciferase assay. The cis-acting elements driving Osgep1 transcription are widely distributed in the Apex gene, in an antisense orientation. The spacer sequence between Osgep1 and Apex has bidirectional promoter activity, and the CCAAT box and Sp1-binding sequence proximal to the transcription initiation site of Osgep1 are involved in transcription of both Osgep1 and Apex genes. A CRE/ATF-like sequence in the Apex gene functions as a repressor of Osgep1 transcription.