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Shared long-range regulatory element...

Xu, Xiaohong.

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Shared long-range regulatory elements coordinate expression of the nAChR beta4/alpha3/alpha5 cluster.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Shared long-range regulatory elements coordinate expression of the nAChR beta4/alpha3/alpha5 cluster./
Author:	Xu, Xiaohong.
Description:	196 p.
Notes:	Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3605.
Contained By:	Dissertation Abstracts International67-07B.
Subject:	Biology, Molecular. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3226718
ISBN:	9780542781834

Shared long-range regulatory elements coordinate expression of the nAChR beta4/alpha3/alpha5 cluster.
Xu, Xiaohong.

Shared long-range regulatory elements coordinate expression of the nAChR beta4/alpha3/alpha5 cluster. - 196 p.

Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3605.

Thesis (Ph.D.)--Case Western Reserve University, 2007.

The nicotinic acetylcholine receptor (nAChR) beta4, alpha3, alpha5 gene cluster encodes several heteromeric transmitter receptor subtypes that are essential for cholinergic synaptic transmission in the 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 have used transgenic methods to investigate long-range transcriptional control of the cluster. A 132kb P1-derived artificial chromosome (PAC) encoding the rat cluster recapitulated the neural- 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 non-coding regions (CNRs) upstream of beta4 and alpha5. Deletion of one of them (CNR4) located 20kb 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.

ISBN: 9780542781834Subjects--Topical Terms:

1017719
Biology, Molecular.

Shared long-range regulatory elements coordinate expression of the nAChR beta4/alpha3/alpha5 cluster.
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245 1 0 $a Shared long-range regulatory elements coordinate expression of the nAChR beta4/alpha3/alpha5 cluster.
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500 $a Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3605.
500 $a Adviser: Evan Deneris.
502 $a Thesis (Ph.D.)--Case Western Reserve University, 2007.
520 $a The nicotinic acetylcholine receptor (nAChR) beta4, alpha3, alpha5 gene cluster encodes several heteromeric transmitter receptor subtypes that are essential for cholinergic synaptic transmission in the 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 have used transgenic methods to investigate long-range transcriptional control of the cluster. A 132kb P1-derived artificial chromosome (PAC) encoding the rat cluster recapitulated the neural- 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 non-coding regions (CNRs) upstream of beta4 and alpha5. Deletion of one of them (CNR4) located 20kb 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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