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SHARED LONG-RANGE REGULATORY ELEMENTS COORDINATE EXPRESSION OF THE NACHR BETA4/ALPHA3/ALPHA5 CLUSTER

Xu, Xiaohong
http://rave.ohiolink.edu/etdc/view?acc_num=case1157660172

Abstract Details

2007, Doctor of Philosophy, Case Western Reserve University, Neurosciences.
The nicotinic acetylcholine receptor (nAChR) â4, á3, á5 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 beat4, 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 â4 and á5. Deletion of one of them (CNR4) located 20kb upstream of beta4 resulted in a dramatic decrease in â4 and á3 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.
Evan Deneris (Advisor)
transcription regulation gene cluster

Recommended Citations

Citations

  • Xu, X. (2007). SHARED LONG-RANGE REGULATORY ELEMENTS COORDINATE EXPRESSION OF THE NACHR BETA4/ALPHA3/ALPHA5 CLUSTER [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1157660172

    APA Style (7th edition)

  • Xu, Xiaohong. SHARED LONG-RANGE REGULATORY ELEMENTS COORDINATE EXPRESSION OF THE NACHR BETA4/ALPHA3/ALPHA5 CLUSTER. 2007. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1157660172.

    MLA Style (8th edition)

  • Xu, Xiaohong. "SHARED LONG-RANGE REGULATORY ELEMENTS COORDINATE EXPRESSION OF THE NACHR BETA4/ALPHA3/ALPHA5 CLUSTER." Doctoral dissertation, Case Western Reserve University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=case1157660172

    Chicago Manual of Style (17th edition)

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© 2006, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.