Characterization of the human Snrpn minimal promoter and cis elements within it

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are caused by loss of gene function of the imprinted genes including Snrpn within a 2 Mb domain on chromosome 15q11-13. Based on microdeletions in PWS and AS patients, a 4.3 sequence around Snrpn promoter/exon 1, together with a 880 bp sequence upstream to Snrpn, are believed to encompass an imprinting control center for the entire 2 Mb domain. We have previously characterized the mouse Snrpn minimal promoter and a 7 bp element (SBE) within it, which is required for its activity. Here we describe the human Snrpn minimal promoter sequence, which is comprised of a 71 bp upstream sequence and 51 bp of exon 1. The SBE, which has been shown to be critical for mouse promoter activity, is also found in the human sequence and absolutely required for promoter activity. Methylation of this element, like in the mouse, prevents the binding of a protein factor and abolishes promoter activity. In addition, the 5′ end of exon 1 must contain cis elements that support promoter activity. In contrast, the 3′ end of exon 1 appears to repress promoter activity. This sequence specifically binds a protein factor which presumably exerts a repressory effect on the promoter. Methylation of this sequence prevents the binding of this protein.