Title

Transcriptional repression by a conserved intronic sequence in the nicotinic receptor alpha3 subunit gene

UMMS Affiliation

Brudnick Neuropsychiatric Research Institute, Department of Psychiatry

Publication Date

5-17-2007

Document Type

Article

Subjects

Animals; Base Sequence; Computational Biology; Conserved Sequence; Electrophoretic Mobility Shift Assay; Gene Expression; Genes, Reporter; Humans; Introns; Mice; Molecular Sequence Data; NIH 3T3 Cells; Nerve Tissue Proteins; Promoter Regions (Genetics); Receptors, Nicotinic; Trans-Activation (Genetics)

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

The genes encoding the nicotinic acetylcholine receptor alpha3, alpha5, and beta4 subunits are genomically clustered. These genes are co-expressed in a variety of cells in the peripheral and central nervous systems. Their gene products assemble in a number of stoichiometries to generate several nicotinic receptor subtypes that have distinct pharmacological and physiological properties. Signaling through these receptors is critical for a variety of fundamental biological processes. Despite their importance, the transcriptional mechanisms underlying their coordinated expression remain to be completely elucidated. By using a bioinformatics approach, we identified a highly conserved intronic sequence within the fifth intron of the alpha3 subunit gene. Reporter gene analysis demonstrated that this sequence, termed "alpha3 intron 5," inhibits the transcriptional activities of the alpha3 and beta4 subunit gene promoters. This repressive activity is position- and orientation-independent. Importantly, repression occurs in a cell type-specific manner, being present in cells that do not express the receptor genes or expresses them at very low levels. Electrophoretic mobility shift assays demonstrate that nuclear proteins specifically interact with alpha3 intron 5 at two distinct sites. We propose that this intronic repressor element is important for the restricted expression patterns of the nicotinic receptor alpha3 and beta4 subunit genes.

DOI of Published Version

10.1074/jbc.M702354200

Source

J Biol Chem. 2007 Jun 29;282(26):19062-70. Epub 2007 May 15. Link to article on publisher's site

Journal/Book/Conference Title

The Journal of biological chemistry

Related Resources

Link to Article in PubMed

PubMed ID

17504758

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