Isolation and characterization of MRF-1, a brain-derived DNA-binding protein with a capacity to regulate expression of myelin basic protein gene.
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.
Haque
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Jefferson Institute of Molecular Medicine, Department of Biochemistry & Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Buchberg
A M
AM
Khalili
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D009687:Nuclear Proteins; D012150:Polymorphism, Restriction Fragment Length; D012333:RNA, Messenger / Q000378:metabolism; D012261:Ribonucleoproteins; D000068103:Serine-Arginine Splicing Factors; D014158:Transcription, Genetic
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012261:Ribonucleoproteins; C499372:SRSF2 protein, mouse; D000068103:Serine-Arginine Splicing Factors