Control of uteroglobin gene expression

Abstract

Eukaryotic nuclear genes are regulated by a complex array of transcription factors that influence RNA polymerase II activity. Included among these factors are the cellular receptors for steroid hormones. The rabbit uteroglobin gene expression is positively stimulated by progesterone, and binding sites for the progesterone receptor have been identified in distal regions of the promoter.

In a recent analysis of the uteroglobin promoter (Rider and Bullock (1988)), a proximal promoter binding activity was identified from nuclear extracts of progesterone-stimulated uterine endometrial tissue. Also discovered was an activity capable of suppressing the DNA binding activity.

In this work, the repressor activity was purified from nuclear extracts. The cause of this activity was found to be fragments of genomic DNA. The promoter binding activity (UGPB) was then further characterised. UGPB-UG200 binding in gel-shift assays was found to be competed out by sheared genomic DNA. Analysis of the UG200 sequence and competition gel-shift assays with poly(dAdT) suggest that UGPB has some affinity for AT-rich stretches of DNA.

There is some evidence that UGPB is induced by both progesterone and, to a lesser extent, oestrogen, but there is still no evidence that it directly affects uteroglobin expression. Many aspects of this DNA binding protein are unlike those of known transcription factors.