Human Cosmc and T‐synthase Genes Are Transcriptionally Regulated by SP1/SP3 Transcription Factors

Abstract

BackgroundCosmc is the specific molecular chaperone for core 1 β3‐galatosyltransferase (T‐synthase), which is the key enzyme for synthesizing the core 1 structure in mucin type O‐glycans. Interestingly, human Cosmc and T‐synthase are ubiquitously and coordinately expressed but vary by cell and tissue type. Genetic mutations in Cosmc have been identified in several human diseases. Recent studies have also shown that both Cosmc and T‐synthase are transcriptionally suppressed in the B cells from some patients with IgA nephropathy. Yet, how these two genes are regulated is unknown.Study ObjectiveIdentify and characterize the promoters for human Cosmc and T‐synthase.MethodsLuciferase reporter assay and chromatin immunoprecipitation (ChIP) analysis.Resultsthe proximal GC‐rich region (CpG island) at the 5′‐flank of human Cosmc (cCpG‐II) which contains two Specificity Protein 1 and 3 (SP1/3) binding sequences has the promoter activity. Similarly, the tCpG in human T‐synase which also contains two SP1/3 sites is the promoter for T‐synthase. Site direct mutagenesis demonstrated that both SP1/3 sequences for Cosmc and T‐synthase are essential to their promoter activity. Furthermore, ChIP analyses confirm that the putative SP1/3 sequence in the promoter associates with the SP1/3 for both Cosmc and T‐synthase.ConclusionHuman Cosmc and T‐synthase are transcriptionally active at a basal level by SP1/SP3.