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Cell type-specific regulation of choline acetyltransferase gene expression - Role of the neuron-restrictive silencer element and cholinergic-specific enhancer

Lonnerberg, Peter and Schoenherr, Christopher J. and Anderson, David J. and Ibáñez, Carlos F. (1996) Cell type-specific regulation of choline acetyltransferase gene expression - Role of the neuron-restrictive silencer element and cholinergic-specific enhancer. Journal of Biological Chemistry, 271 (52). pp. 33358-33365. ISSN 0021-9258.

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This study demonstrates the presence of positive and negative regulatory elements within a 2336-base pair-long region of the rat choline acetyltransferase (ChAT) gene promoter that cooperate to direct cell type-specific expression in cholinergic cells. A 21-base pair-long neuron-restrictive silencer element (NRSE) was identified in the proximal part of this region. This element was recognized by the neuron-restrictive silencer factor (NRSF), previously shown to regulate expression of other neuron-specific genes. The ChAT NRSE was inactive in both cholinergic and non-cholinergic neuronal cells, but repressed expression from a heterologous promoter in non-neuronal cells. Specific deletion of this element allowed ChAT gene promoter activity in non-neuronal cells, and overexpression of NRSF repressed ChAT gene promoter activity in cholinergic cells. The distal part of the ChAT gene promoter showed cholinergic-specific enhancing activity, which stimulated promoter activity in cholinergic cells, but was inactive in non-cholinergic neuronal and non-neuronal cells. This enhancer region suppressed the activity of the ChAT NRSE in cholinergic cells, even after NRSF overexpression. Thus, at least two kinds of regulatory elements cooperate to direct ChAT gene expression to cholinergic neurons, namely a neuron-restrictive silencer element and a cholinergic-specific enhancer.

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Anderson, David J.0000-0001-6175-3872
Additional Information:Copyright © 1996 by the American Society for Biochemistry and Molecular Biology. Received for publication, June 13, 1996, and in revised form, September 13, 1996). We thank Ann-Sofie Nilsson for technical assistance. We also thank Drs. David Hammond and Alfred Heller for the SN6 cells and Dr. Edgar F. Salazar-Grueso for the motor neuron cell line. This work was supported by the Swedish Medical Research Council, Centrala försöksdjurs-nämnden, and the Karolinska Institute. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) X92751.
Issue or Number:52
Record Number:CaltechAUTHORS:LONjbc96
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:7252
Deposited By: Lindsay Cleary
Deposited On:23 Jan 2007
Last Modified:09 Mar 2020 13:18

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