Genomic organization of human GMEB-1 and rat GMEB-2: structural conservation of two multifunctional proteins.

The glucocorticoid modulatory element binding proteins 1 and 2 (GMEB-1 and GMEB-2) are of interest both for their multiple activities (e.g. modulation of transactivation by the glucocorticoid receptor and initiation of parvovirus replication) and their membership in the emerging family of KDWK proteins. The genomic sequence of these proteins was desired in order to begin studies on the control of GMEB expression and to pursue previous evidence for significant homologies between the GMEBs. We now report the genomic sequence of human GMEB-1 and rat GMEB-2. The structure of both genes, including portions of the introns, is highly conserved. However, GMEB-1 and GMEB-2 were found to reside on chromosomes 1 and 20, respectively, demonstrating that they are encoded by distinctly different genes. Several isoforms of the GMEBs have been reported or detected in this study, and the splicing patterns were determined. The tissue distribution of each GMEB is not the same and is highest in fetal and developing tissues, consistent with previous suggestions that both homo- and hetero-oligomers may possess biological activity. The promoter region of both genes has been identified and both display high levels of transcription activity in transiently transfected cells when fused upstream of a promoterless reporter. These results indicate that the GMEBs are proteins that evolved from a single parent gene, have been highly conserved since the divergence of rats and humans and probably play important roles in development and differentiation.