Differentiation and fiber type-specific activity of a muscle creatine kinase intronic enhancer
Differentiation of oligodendrocyte progenitors into mature oligodendrocytes involves the timely, cell-type specific expression of a number of different genes. Among these, the expression of the myelin basic protein (MBP) gene closely parallels the course of oligodendrocyte differentiation. To understand how transcription of the myelin basic protein gene is controlled, binding to the distal end of the 5' flanking sequence of the MBP gene was investigated. Specific protein-DNA complexes were localized to an AP-1-like element located between -1230 and -1240. The protein-DNA complexes formed at this site were shown to change as the cells differentiated. In undifferentiated cells two complexes were formed but, as the cells differentiated, binding was nearly completely lost. One of the two complexes was shown to contain a member of the fos family of transcription factors but no jun family members were involved. Mutation of the AP-1-like site resulted in loss of the complex and a change in expression of a reporter construct driven by the mutated promoter sequence. These results demonstrate a role for the AP-1-like site in repression of MBP gene expression in oligodendrocyte progenitor cells.