AP-1 and T3RE cis elements operate as a functional unit in the transcriptional control of the human malic enzyme gene.

The human malic enzyme (hME) promoter contains an inverted palindromic (IP4) 3,5,3'-triiodo-thyronine (T3) response element (T3RE) 15bp downstream from an activating protein-1 (AP-1) site. The purpose of this study was to analyze the functional relationship between both cis-acting elements. The following observations indicate that these two elements operate as a functional unit in controlling the human ME gene:T3 failed to stimulate transcription above the basal levels in cells overexpressing either TRb or TRb/retinoid acid receptor (RXR), indicating that TRbeta acts primarily as a transcriptional repressor in the context of the hME. Moreover, the finding of a repressive effect of TRbeta without DNA binding suggests the existence of both DNA-dependent and independent mechanisms of TRbeta-induced repression of transcription.