THE HUMAN MYELIN BASIC-PROTEIN GENE IS INCLUDED WITHIN A 179-KILOBASETRANSCRIPTION UNIT - EXPRESSION IN THE IMMUNE AND CENTRAL NERVOUS SYSTEMS

Two human Golli (for gene expressed in the oligodendrocyte lineage)-MB P (for myelin basic protein) cDNAs have been isolated from a human oli godendroglioma cell line. Analysis of these cDNAs has enabled us to de termine the entire structure of the human Golli-MBP gene. The Golli-MB P gene, which encompasses the MBP transcription unit, is almost-equal- to 179 kb in length and consists of 10 exons, seven of which constitut e the MBP gene. The human Golli-MBP gene contains two transcription st art sites, each of which gives rise to a family of alternatively splic ed transcripts. At least two Golli-MBP transcripts, containing the fir st three exons of the gene and one or more MBP exons, are produced fro m the first transcription start site. The second family of transcripts contains only MBP exons and produces the well-known MBPs. In humans, RNA blot analysis revealed that Golli-MBP transcripts were expressed i n fetal thymus, spleen, and human B-cell and macrophage cell lines, as well as in fetal spinal cord. These findings clearly link the express ion of exons encoding the autoimmunogen/encephalitogen MBP in the cent ral nervous system to cells and tissues of the immune system through n ormal expression of the Golli-MBP gene. They also establish that this genetic locus, which includes the MBP gene, is conserved among species , providing further evidence that the MBP transcription unit is an int egral part of the Golli transcription unit and suggest that this struc tural arrangement is important for the genetic function and/or regulat ion of these genes.