HORMONE-INDUCED RECRUITMENT OF SP1 MEDIATES ESTROGEN ACTIVATION OF THE RABBIT UTEROGLOBIN GENE IN ENDOMETRIAL EPITHELIUM

Steroid hormones activate gene expression by interaction of their rece ptors with hormone-responsive DNA elements and tissue-specific or ubiq uitous factors. To monitor the molecular changes on the promoter of th e rabbit uteroglobin gene during early pseudopregnancy in vitro, we ha ve applied the genomic footprinting methodology to endometrial tissue, Estrogen induction results in the simultaneous occupancy of an estrog en-re sponsive element and an adjacent GC/GT box in the promoter, DNA binding assays demonstrate that the corresponding regulatory factors a re the ligand-induced estrogen receptor and the ubiquitous transcripti on factor Sp1, Both factors functionally synergize in primary endometr ial cells, showing that the GC/GT box is an essential part of a compos ite estrogen-responsive unit, However, the estrogen receptor and Sp1 d o not bind cooperatively to their sites in vitro, suggesting that othe r mechanisms might be responsible for the hormone-dependent binding of Sp1 in vivo. Since hormone treatment leads to the appearance of a dis tinct DNase I-hypersensitive site over the promoter chromatin, an estr ogen-induced change in the local chromatin structure could facilitate binding of Sp1 in vivo.