ISOLATION AND CHARACTERIZATION OF MRF-1, A BRAIN-DERIVED DNA-BINDING PROTEIN WITH A CAPACITY TO REGULATE EXPRESSION OF MYELIN BASIC-PROTEINGENE

The 5'-flanking region of the myelin basic protein (MBP) contains seve ral regulatory elements that differentially contribute to the cell typ e specific transcription of MBP in cells derived from the central nerv ous system. The distal regulatory element, termed MB3, had previously been shown to have characteristics of a cell type-specific enhancer el ement and bind to multiple brain-derived nuclear proteins in vitro. We now report the isolation of a recombinant cDNA clone, named myelin re gulatory factor-1 (MRF-1) from a mouse brain expression library that e ncodes a novel protein which interacts with the MB3 domain. Computer-a ssisted analysis of MRF-1 revealed substantial sequence homology in th e central and the COOH-terminal regions of this protein with the previ ously identified splicing factor SC35. Co transfection studies indicat ed that MRF-1 increases transcription of the MBP promoter in glial cel ls and that this activation requires an intact MRF-1-binding site with in the MB3 region. MRF-1 cDNA hybridized to three RNA species 1.8, 2.5 , and 3.0 kilobases which are expressed in all tissues analyzed. The g ene encoding MRF-1 is located on the distal half of mouse chromosome 1 1 in a region where the human homolog would be predicted to reside on human chromosome 17.