The transcriptional regulator Yin Yang 1 activates the myelin PLP gene

Inauguration of the myelin program in developing oligodendrocytes requires the activation of those genes that encode the myelin proteins and the enzym es responsible for the synthesis and degradation of myelin lipids. An activ ator of the most abundantly expressed myelin protein, proteolipid protein ( PLP), has been identified in a yeast one-hybrid system. The ubiquitously ex pressed zinc finger protein Yin Yang 1 (YY1) recognizes the myelin PLP prom oter in vitro and in vivo. When overexpressed in an oligodendrocyte cell li ne, YY1 enhances transcription of the PLP promoter. A truncated version of YY1 that includes only the four zinc finger domains has little effect. The binding site for YY1 in the PLP promoter (site 3) fits the YY1 consensus si te and DNA-protein complexes containing site 3 can be supershifted with an antibody directed against YY1 protein. Moreover, oligonucleotides with a mu tated version of the PLP promoter site 3 are unable to bind to nuclear prot eins or to compete for binding in a gel shift system. Finally, mutation of this site greatly reduces the activity of a I-kb PLP promoter region in tra nsfected glial cells. Our results suggest that PLP is a target gene for the transcriptional regulator YY1. This versatile transcription factor and nuc lear matrix protein may boost transcription of the PLP gene to meet the dem ands of actively myelinating oligodendrocytes.