ALTERATIONS IN THE CHROMATIN STRUCTURE OF THE DISTAL PROMOTER REGION OF THE BOVINE OXYTOCIN GENE CORRELATE WITH OVARIAN EXPRESSION

The mechanisms regulating the expression of the neuropeptide hormone g ene oxytocin have not yet been elucidated in detail. The binding of th e orphan receptor Ad4BP, the bovine homolog of steroidogenic factor-1 (SF-1), which is correlated with in vivo oxytocin transcription in the luteinizing granulosa cells of the bovine corpus luteum, is not suffi cient to explain the transcriptional up-regulation in these cells. The refore, me started experiments to identify other regions of the oxytoc in locus that are involved in gene activation. The study presented her e is the very first investigation of DNA methylation and chromatin str ucture in the distal promoter region of the bovine oxytocin gene. We s how that this region is tissue-specifically hypomethylated in bovine g ranulosa cells. Upon stimulation of the cells with the adenylate cycla se-activator forskolin, a DNase I-hypersensitive site is induced in th e distal promoter region. Additionally, we find binding of a monomeric nuclear orphan receptor directly within the region of inducible DNase I sensitivity; this factor is not identical to Ad4BP/SF-1. This study identifies a region in the bovine oxytocin distal promoter where tiss ue-specific changes in DNA methylation and chromatin structure correla te with high induction of oxytocin gene transcription, and suggests th at the binding of transcription factors to this region may be importan t for the upregulation of oxytocin gene expression.