GENOMIC ELEMENT WITHIN THE 3RD INTRON OF THE HUMAN OXYTOCIN RECEPTOR GENE MAY BE INVOLVED IN TRANSCRIPTIONAL SUPPRESSION

The human oxytocin receptor (OTR) gene comprises a large (>10 kb) thir d intron between the regions encoding the transmembrane domains six an d seven. It has been shown for other genes that transcriptional contro l elements may reside within such introns, and that these may correlat e with changes in the methylation status of the DNA. Methylation mappi ng indeed indicated that within this third intron there was a region w hich appeared to be hypermethylated in non-expressing tissues, but rel atively hypomethylated in the myometrium of the cycle and at term, whe n the OTR gene is upregulated. We then employed in vitro nuclear prote in-DNA binding assays to evaluate the importance of this region in the control of the human OTR gene. As source of nuclear proteins we have compared a non-expressing tissue, human peripheral blood leucocytes, w ith human myometrium from the cycle (low expression) and from term pre gnancy (high expression). It could be shown that a specific motif of c a. 10-15 nucleotides close to the middle of the third intron specifica lly binds nuclear proteins correlating with the down-regulated state o f the gene. The accumulated data suggest that this intronic element is specifically binding nuclear protein(s) associated with a suppression of OTR gene activity. (C) 1997 Elsevier Science Ireland Ltd.