EXPRESSION OF THE RAT GROWTH-HORMONE GENE IS UNDER THE INFLUENCE OF A CELL-TYPE-SPECIFIC SILENCER ELEMENT

We have previously shown that a cell-type-specific negative-regulatory element, or silencer, acts to specifically restrict rat-growth-hormone(rGH)-promoter activity to pituitary cells. Here we report a detailed characterization of this element. The activity of the silencer is dependent on its position relative to the promoter. The negative regulatory effect can be diminished by cotransfection with a high-copy-number, silencer-containing competitor plasmid, suggesting that the function of the element is mediated by specific binding of a trans-acting negative-regulatory factor. The minimal region required for silencer function is contained between positions -309 and -266 relative to the start of the rGH mRNA. The specific interaction of a nuclear protein from non-pituitary cells with this rGH DNA segment was shown by DNaseI as well as dimethylsulfate methylation-interference footprinting. A detailed examination of the DNA-binding site for that protein clearly suggest that it belongs to the NF1 family of transcription factors.