Functional interaction between the glucocorticoid receptor and C/EBP-beta.

Abstract

Glucocorticoid receptor (GR) is a ligand activated sequence specific transcription factor that belongs to the nuclear receptor superfamily. Most often GR regulates transcription through binding to glucocorticoid DNA response elements (GREs) found in the regulatory regions of target genes. Regulation of transcription by GR usually occurs in a combination with other heterologous transcription factors whose DNA response elements are found in proximity of GREs in the gene regulatory regions. The Herpes Simplex Virus thymidine kinase (HSV tk) proximal promoter contains two DNA binding sites for Sp1, and one "CCAAT" DNA motif. Surprisingly, when GR was transiently co-transfected with a CAT reporter gene driven by the HSV tk promoter, it induced HSV tk transcription 5 fold in response to dexamethasone in the absence of any apparent GREs. Activation of HSV tk transcription was dexamethasone dependent, as RU 486, a GR antagonist was unable to activate transcription. Activation of HSV tk was also GR specific as androgen receptor was unable to activate HSV tk transcription following DHT treatment. To map the region of GR responsible for GRE independent activation of HSV tk transcription, several different GR expression constructs were used. (Abstract shortened by UMI.)