A role for an AP-1-like site in the expression of the myelin basic proteingene during differentiation

Differentiation of oligodendrocyte progenitors into mature oligodendrocytes involves the timely, cell-type specific expression of a number of differen t genes. Among these, the expression of the myelin basic protein (MBP) gene closely parallels the course of oligodendrocyte differentiation. To unders tand how transcription of the myelin basic protein gene is controlled, bind ing to the distal end of the 5' flanking sequence of the MBP gene was inves tigated. Specific protein-DNA complexes were localized to an AP-1-like elem ent located between -1230 and -1240. The protein-DNA complexes formed at th is site were shown to change as the cells differentiated. In undifferentiat ed cells two complexes were formed but, as the cells differentiated, bindin g 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 memb ers were involved. Mutation of the AP-l-like site resulted in loss of the c omplex and a change in expression of a reporter construct driven by the mut ated promoter sequence. These results demonstrate a role for the AP-1-like site in repression of MBP gene expression in oligodendrocyte progenitor cel ls. (C) 2001 ISDN. Published by Elsevier Science Ltd. All rights reserved.