ArticleMolecular and cellular biology2006
Shared long-range regulatory elements coordinate expression of a gene cluster encoding nicotinic receptor heteromeric subtypes.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- Response to Transdermal Selegiline Smoking Cessation Therapy and Markers in the 15q24 Chromosomal Region.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2015Trial
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- Novel Transgenic Zebrafish Lines to Study the CHRNA3-B4-A5 Gene Cluster.Developmental neurobiology · 2025Article
- Evidence for Association Between Low Frequency Variants in CHRNA6/CHRNB3 and Antisocial Drug Dependence.Behavior genetics · 2016Article
- Spinocerebellar ataxia type 6 protein aggregates cause deficits in motor learning and cerebellar plasticity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Two potential hookworm DAF-16 target genes, SNR-3 and LPP-1: gene structure, expression profile, and implications of a cis-regulatory element in the regulation of gene expression.Parasites & vectors · 2015Article
- A discrete transition zone organizes the topological and regulatory autonomy of the adjacent tfap2c and bmp7 genes.PLoS genetics · 2015Article
- Alternative CHRNB4 3'-UTRs mediate the allelic effects of SNP rs1948 on gene expression.PloS one · 2013Article
- Genetic dissection of medial habenula-interpeduncular nucleus pathway function in mice.Frontiers in behavioral neuroscience · 2013Article
- Regulatory modules function in a non-autonomous manner to control transcription of the mbp gene.Nucleic acids research · 2011Article
- A transcriptional regulatory element critical for CHRNB4 promoter activity in vivo.Neuroscience · 2010Article
- The nicotinic acetylcholine receptor CHRNA5/A3/B4 gene cluster: dual role in nicotine addiction and lung cancer.Progress in neurobiology · 2010Review
- From smoking to lung cancer: the CHRNA5/A3/B4 connection.Oncogene · 2010Review
- Association and interaction analysis of variants in CHRNA5/CHRNA3/CHRNB4 gene cluster with nicotine dependence in African and European Americans.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2010Article
- Aberrant DNA methylation links cancer susceptibility locus 15q25.1 to apoptotic regulation and lung cancer.Cancer research · 2010Article
- Temporally- and spatially-regulated transcriptional activity of the nicotinic acetylcholine receptor beta4 subunit gene promoter.Neuroscience · 2010Article
- ASCL1 regulates the expression of the CHRNA5/A3/B4 lung cancer susceptibility locus.Molecular cancer research : MCR · 2010Article
- The alpha 3 subunit gene of the nicotinic acetylcholine receptor is a candidate gene for ethanol stimulation.Genes, brain, and behavior · 2009Article
- Mammalian nicotinic acetylcholine receptors: from structure to function.Physiological reviews · 2009Review
- The CHRNA5/A3/B4 gene cluster variability as an important determinant of early alcohol and tobacco initiation in young adults.Biological psychiatry · 2008Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The nicotinic acetylcholine receptor (nAChR) beta4/alpha3/alpha5 gene cluster encodes several heteromeric transmitter receptor subtypes that are essential for cholinergic synaptic transmission in adrenal gland, autonomic ganglia, pineal gland, and several nuclei in the central nervous system. However, the transcriptional mechanisms coordinating expression of these subunit genes in different cell populations are unknown. Here, we used transgenic methods to investigate long-range transcriptional control of the cluster. A 132-kb P1-derived artificial chromosome (PAC) encoding the rat cluster recapitulated the neurally- and endocrine-restricted expression patterns of the endogenous beta4/alpha3/alpha5 genes. Mutation of ETS factor binding sites in an enhancer, beta43', embedded in the beta4 3'-untranslated exon resulted in greatly diminished beta4, alpha3, and alpha5 expression in adrenal gland and to a lesser extent in the superior cervical ganglion (SCG) but not in other tissues. Phylogenetic sequence analyses revealed several conserved noncoding regions (CNRs) upstream of beta4 and alpha5. Deletion of one of them (CNR4) located 20 kb upstream of beta4 resulted in a dramatic decrease in beta4 and alpha3 expression in the pineal gland and SCG. CNR4 was sufficient to direct LacZ transgene expression to SCG neurons, which express the endogenous beta4alpha3alpha5 subunits, and pineal cells, which express the endogenous beta4alpha3 combination. Finally, CNR4 was able to direct transgene expression to major sites of expression of the endogenous cluster in the brain. Together, our findings support a model in which cell type-specific shared long-range regulatory elements are required for coordinate expression of clustered nAChR genes.
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