Glucocorticoid inhibition of transcription from episomal proopiomelanocortin gene promoter.

Glucocorticoid hormones alter transcription of specific genes. Glucocorticoid-stimulated genes have been especially useful in unraveling molecular events responsible for positive gene regulation in mammals. The gene encoding proopiomelanocortin (POMC), which is under feedback inhibition by glucocorticoids, provides a model system to study negative gene regulation. Using an episomal bovine papilloma virus vector, we now demonstrate that a 769-base-pair fragment containing the rat POMC promoter is sufficient to confer glucocorticoid inhibition. Transcription from the episomal POMC promoter starts at the same site and is inhibited by glucocorticoids to the same extent as POMC transcription in the anterior pituitary. Glucocorticoid inhibition is specific for POMC transcripts; neither bovine papilloma virus nor cellular actin mRNAs are affected by glucocorticoids. Thus, the episomal bovine papilloma virus/POMC system can be used to study the relationship between negative regulation of POMC transcription and chromatin structure.