Isolation and characterization of MRF-1, a brain-derived DNA-binding protein with a capacity to regulate expression of myelin basic protein gene

Abstract

The 5'-flanking region of the myelin basic protein (MBP) contains several regulatory elements that differentially contribute to the cell type-specific transcription of MBP in cells derived from the central nervous system. The distal regulatory element, termed MB3, had previously been shown to have characteristics of a cell type-specific enhancer element and bind to multiple brain-derived nuclear proteins in vitro. We now report the isolation of a recombinant cDNA clone, named myelin regulatory factor-1 (MRF-1) from a mouse brain expression library that encodes a novel protein which interacts with the MB3 domain. Computer-assisted analysis of MRF-1 revealed substantial sequence homology in the central and the COOH-terminal regions of this protein with the previously identified splicing factor SC35. Cotransfection studies indicated that MRF-1 increases transcription of the MBP promoter in glial cells and that this activation requires an intact MRF-1-binding site within 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 gene encoding MRF-1 is located on the distal half of mouse chromosome 11 in a region where the human homolog would be predicted to reside on human chromosome 17.