Sequence Similarities of Myelin Basic Protein Promoters from Mouse and Shark: Implications for the Control of Gene Expression in Myelinating Cells

Abstract

Abstract:To better understand the cell type-specific and coordinated regulation of the myelin protein genes, we cloned and sequenced the shark myelin basic protein (MBP) promoter. An alignment of the shark sequence with the corresponding mouse sequence showed striking similarities. These similarities, together with the results from expression experiments, define two major regions (A and B) within the MBP promoter. Region A is located immediately 5' to the transcription initiation sites and includes five sequences thought to be cis-acting domains. These domains include two boxes of 13 and 12 nucleotides, respectively, separated from each other by 10 nucleotides, an MBP enhancer, and GC, CCAAT, and TATA boxes. Region A also contains a putative exon that codes for 35 amino acids of an unidentified polypeptide. Region B, which is located adjacent to the 5' end of region A, contains two boxes that are 10 and 1 I nucleotides long, respectively, and are identical in mouse and shark. We have previously cloned and sequenced the shark glycoprotein zero (Po) promoter. A comparison between the sequences of the rat and shark Po promoters shows three conserved regions in addition to CCAAT and TATA boxes. The shark Po promoter is active in the CNS and PNS, and contains a sequence of 13 nucleotides that is located at -159 from the initiation of transcription and is similar to that of the MBP enhancer. The mammalian Po promoter is active exclusively in the adult PNS and contains a sequence similar to that of the MBP enhancer located adjacent to the 3' side of the transcription initiation site. Sequence similarities and differences between the promoters of the mammalian and shark myelin protein genes will help to identify the basis for the cell type-specific and coordinated expression of these genes. Key Words: Myelin protein genes-Myelin basic protein promoter-Po promoter. Fors L. et al. Sequence similarities of myelin basic protein promoters from mouse and shark: Implications for the control ofgene expression in myelinating cells. J. Neurochern. 60, 513-521 (1993).

The human myelin basic protein gene is included within a 179-kilobase transcription unit: expression in the immune and central nervous systems.

“…This segment is denoted as exon 5a and corresponds to the Golli-MBP exon 5a/Mbp exon la of the mouse gene (13,16). Interestingly, this is also a region of high sequence conservation in the genomes of mouse, human, and shark (17).…”

The evolution of Olig genes and their roles in myelination

“…Multiple alignment of a vertebrate specific cis-regulatory element in exon 5 of Golli-Mbp genes. Fragments of exon 5 from human, mouse, rat, chick, zebrafish (Li et al , 2007) and shark (Fors et al , 1993) were aligned using BioEdit/ClustalW software. A conserved cis-regulatory element including an E-Box and an HMG (high mobility group) binding domain is underlined.…”

Regulation of Oleoyl‐CoA Synthesis in the Peripheral Nervous System: Demonstration of a Link with Myelin Synthesis

“…The PMP-22 promoter 1 sequence was from Suter et al (1994). References to other myelin protein gene promoters are given by Nave and Lemke (1991) and Fors et al (1993). FIG.…”