Myelin basic protein gene contains separate enhancers for oligodendrocyte and Schwann cell expression.
The DNA sequence between position +36 and -1907 of the murine myelin basic protein gene contains the enhancer and promoter elements necessary for abundant and cell specific expression in transgenic mice. Surprisingly, the pattern of expression promoted by this DNA fragment is a subset of that exhibited by the endogenous myelin basic protein (MBP) gene. Fusion genes prepared with this promoter/enhancer and a Lac Z reporter gene are expressed only in oligodendrocytes and not in Schwann cells, whereas the endogenous MBP gene is expressed in both cell types. The level of transgene expression measured by nuclear run-on experiments is very substantial and rivals that of the endogenous MBP gene. Furthermore, this 1.9-kb DNA fragment directs transcription on the same (or very similar) developmental schedule as the endogenous gene. These results indicate that the MBP promoter/enhancer sequences are at least tripartite: a core promoter, the oligodendrocyte enhancer elements, and a third component that either expands the specificity of the oligodendrocyte enhancer to include Schwann cells or acts independently to specifically stimulate transcription in Schwann cells.
Gow
A
A
Brookdale Center for Molecular Biology, Mount Sinai Medical Center, New York 10029-6574.
Friedrich
V L
VL
Lazzarini
R A
RA
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000502:physiology*; D002467:Cell Nucleus / Q000502:physiology; D004247:DNA / Q000235:genetics* / Q000302:isolation & purification; D004742:Enhancer Elements, Genetic; D015870:Gene Expression; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000235:genetics*; D009836:Oligodendroglia / Q000502:physiology*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015183:Restriction Mapping; D012583:Schwann Cells / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D004676:Myelin Basic Protein; D011993:Recombinant Fusion Proteins; D004247:DNA; D001616:beta-Galactosidase