Multiple neuron-specific enhancers in the gene coding for the human neurofilament light chain.
To define DNA regions involved in the neuron-specific expression of the neurofilament light (NF-L) gene, we generated transgenic mice bearing different NF-L constructs. A 4.9-kilobase human NF-L fragment including -292 base pairs of 5'-flanking sequences contained sufficient elements for nervous system expression in transgenic mice. Deletion of introns 1 and 2 from this 4.9-kilobase DNA fragment resulted in reduced levels of transgene expression in the cortex, while deletion of intron 3 had little effect. Both introns 1 and 2 could act independently as enhancers to confer neuronal expression of the basal heat shock promoter (hsp68) fused to lacZ in transgenic mice. The hNF-L basal promoter (-292 base pairs) was found to contain elements for directing neuronal expression of either the lacZ reporter gene or an intronless hNF-L construct. Sequence comparison revealed that intron 1, intron 2, and the basal human NF-L promoter all contain an ETS-like motif, CAGGA, present in a variety of genes expressed in the nervous system.
Centre for Research in Neuroscience, McGill University, Montreal General Hospital Research Institute, Quebec, Canada.
G
G
Charron
L G
LG
Guy
M
M
Bazinet
J P
JP
Julien
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004622:Embryo, Mammalian; D004742:Enhancer Elements, Genetic; D005091:Exons; D005260:Female; D006801:Humans; D007438:Introns; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016900:Neurofilament Proteins / Q000096:biosynthesis* / Q000235:genetics*; D009474:Neurons / Q000502:physiology*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000096:biosynthesis; D015183:Restriction Mapping; D017384:Sequence Deletion; D001616:beta-Galactosidase / Q000096:biosynthesis
D017931:DNA Primers; D016900:Neurofilament Proteins; D011994:Recombinant Proteins; C044882:neurofilament protein L; D001616:beta-Galactosidase