Identification of virtual signal transducers and activators of transcription response elements in the human insulin receptor gene promoter

Abstract

In this study, we look for the existence of signal transducers and activators of transcription response elements (STATREs) in the human insulin receptor (hIR) gene promoter and their possible relation with the estradiol-provoked transcriptional repression of the hIR gene and cellular insulin resistance in U-937 human promonocytic cells. Potential STATREs in the region from −1819 to −271 bp of the hIR gene promoter were identified by their homology with the consensus STATRE (5′TTCnnnGAA3′) using the SEQFIND programme developed in our laboratory. We located five virtual STATRE-like sites: [(I): −1472/−1464], [(II): −1548/−1540], [(III): −1552/−1544], [(IV): −1587/−1579] and [(V): −1678/−1670] showing a difference of only one base from this consensus. These STATREs-like sites were situated between 33 bp upstream the 5′ half-element of the estrogen response element 1 (ERE1)-like (−1430/−1418) and 102 bp upstream the 5′ half-element of the ERE2-like (−1567/−1555) complexed with AP-1-like sites. A principal complex constituted by STATREs (II–IV) the ERE2 and AP-1 sites (IV and V) was located between −1587/−1540 bp of the hIR gene promoter.

In conclusion, these results represent the first identification of virtual STATREs in the hIR gene promoter. These STATREs appear to be specifically located in the surroundings of the two EREs overlapped by various AP-1 sites. These complexes could mediate crosstalk among STATs, estrogen receptor β (ERβ), and AP-1 regulating the ERβ-mediated transcriptional repression of the hIR gene and insulin resistance in U-937 cells.