NDLI: Identification of evolutionarily conserved, functional noncoding elements in the promoter region of the sodium channel gene SCN8A

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Identification of evolutionarily conserved, functional noncoding elements in the promoter region of the sodium channel gene SCN8A

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Identification of evolutionarily conserved, functional noncoding elements in the promoter region of the sodium channel gene SCN8A

Content Provider	Springer Nature Link
Author	Drews, Valerie L. Shi, Kehui Haan, Georgius Meisler, Miriam H.
Copyright Year	2007
Abstract	SCN8A is a major neuronal sodium channel gene expressed throughout the central and peripheral nervous systems. Mutations of SCN8A result in movement disorders and impaired cognition. To investigate the basis for the tissue-specific expression of SCN8A, we located conserved, potentially regulatory sequences in the human, mouse, chicken, and fish genes by 5′ RACE of brain RNA and genomic sequence comparison. A highly conserved 5′ noncoding exon, exon 1c, is present in vertebrates from fish to mammals and appears to define the ancestral promoter region. The distance from exon 1c to the first coding exon increased tenfold during vertebrate evolution, largely by insertion of repetitive elements. The mammalian gene acquired three novel, mutually exclusive noncoding exons that are not represented in the lower vertebrates. Within the shared exon 1c, we identified four short sequence elements of 10-20 bp with an unusually high level of evolutionary conservation. The conserved elements are most similar to consensus sites for the transcription factors Pou6f1/Brn5, YY1, and REST/NRSF. Introduction of mutations into the predicted Pou6f1 and REST sites reduced promoter activity in transfected neuronal cells. A 470-bp promoter fragment containing all of the conserved elements directed brain-specific expression of the LacZ reporter in transgenic mice. Transgene expression was highest in hippocampal neurons and cerebellar Purkinje cells, consistent with the expression of the endogenous gene. The compact cluster of conserved regulatory elements in SCN8A provides a useful target for molecular analysis of neuronal gene expression.
Starting Page	723
Ending Page	731
Page Count	9
File Format	PDF
ISSN	09388990
Journal	Mammalian Genome
Volume Number	18
Issue Number	10
e-ISSN	14321777
Language	English
Publisher	Springer-Verlag
Publisher Date	2007-10-09
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Zoology Anatomy Cell Biology
Content Type	Text
Resource Type	Article
Subject	Genetics

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Identification of evolutionarily conserved, functional noncoding elements in the promoter region of the sodium channel gene SCN8A

Identification of evolutionarily conserved, functional noncoding elements in the promoter region of the sodium channel gene SCN8A

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