Chromatin structure and transcriptional activity of MAG

Myelin associated glycoprotein (MAG) is an essential component of the periaxonal architecture of the myelin sheath. Because of its potent neurite growth repressive activity, MAG is also likely to play an important role in axonal guidance during the CNS development, and to be responsible for abortive neuronal regeneration in adult CNS. The MAG gene chromatin from approximately 1.6 to +0.6 kb features MNase hypersensitivity that maydelineate the gene control region. The proximal upstream region of the gene is organized into an array of five nucleosomes with hypersensitive linkers. The core promoter is located within the first upstream linker that becomes highly hypersensitive in the course of oligodendrocyte differentiation. The adjacent upstream region contains positive and negative enhancers that are likely to streamline oligodendrocyte specific expression of the gene. The TATA-less core promoter contains novel, as yet uncharacterized initiator elements that direct the assembly of transcriptional complexes. The promoter appears to be controlled by both, the addition of activating trans-factors and the removal of inhibitory trans-factors as progenitor cells differentiate into mature oligodendrocyte. The developmental activation of the gene is also concomitant with profound DNA demethylation that may provide auxiliary regulatory mechanisms. Hence, the upregulation of the MAG gene in differentiating oligodendrocytes entails chromatin remodeling as well as changes in the assortment of nuclear trans-factors.