CHARACTERIZATION OF THE PROMOTER REGION OF HUMAN STEROID SULFATASE - A GENE WHICH ESCAPES X-INACTIVATION

The human X-linked steroid sulfatase gene (STS) was among the first ge nes shown to escape X inactivation. At least fourteen genes regulated in this fashion have now been recognized. They are dispersed into seve ral regions of the X chromosome and may be controlled in a locus speci fic manner. Studies of the promoters of these genes could provide insi ghts into the mechanism of X inactivation, however little information of this nature is currently available. For this reason we examined 5'f lanking sequences of the human STS gene for promoter function. Four tr anscription start sites scattered over a 50bp region were identified. Functional domains of this TATA-less and GC poor promoter were identif ied by study of a series of terminal and internal deletions. A putativ e promoter sequence was identified which by itself exhibits little or no basal activity. However when combined with upstream regulatory elem ents, this segment showed weak but reproducible activity In a CAT (chl oramphenicol acetyltransferase) reporter assay. Several regulatory dom ains acting as enhancers and repressors were subsequently identified. The relationship of this 5' sequence to the ability of the STS gene to escape X-inactivation is discussed.