Shimojo, Masahito and Paquette, Alice J. and Anderson, David J. and Hersh, Louis B. (1999) Protein Kinase A Regulates Cholinergic Gene Expression in PC12 Cells: REST4 Silences the Silencing Activity of Neuron-Restrictive Silencer Factor/REST. Molecular and Cellular Biology, 19 (10). pp. 6788-6795. ISSN 0270-7306 http://resolver.caltech.edu/CaltechAUTHORS:SHImcb99
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The role of protein kinase A in regulating transcription of the cholinergic gene locus, which contains both the vesicular acetylcholine transporter gene and the choline acetyltransferase gene, was investigated in PC12 cells and a protein kinase A-deficient PC12 mutant, A126.1B2, in which transcription of the gene is reduced. The site of action of protein kinase A was localized to a neuron-restrictive silencer element/repressor element 1 (NRSE/RE-1) sequence within the cholinergic gene. Neuron-restrictive silencer factor (NRSF)/RE-1-silencing transcription factor (REST), the transcription factor which binds to NRSE/RE-1, was expressed at similar levels in both PC12 and A126.1B2 cells. Although nuclear extracts containing NRSF/REST from A126.1B2 exhibited binding to NRSE/RE-1, nuclear extracts from PC12 cells did not. The NRSF/REST isoform REST4 was expressed in PC12 cells but not in A126.1B2. REST4 inhibited binding of NRSF/REST to NRSE/RE-1 as determined by gel mobility shift assays. Coimmunoprecipitation was used to demonstrate interaction between NRSF/REST and REST4. Expression of recombinant REST4 in A126.1B2 was sufficient to transcriptionally activate the cholinergic gene locus. Thus, in PC12 cells, protein kinase A promotes the production of REST4, which inhibits repression of the cholinergic gene locus by NRSF/REST.
|Additional Information:||Copyright © 1999, American Society for Microbiology. Received 29 March 1999/Returned for modification 22 April 1999/Accepted 19 July 1999 This research was supported in part by grants from the National Institute on Aging (AG05893 and AG05144). A.J.P. is a recipient of an NIH predoctoral training grant.|
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|Deposited On:||10 Apr 2006|
|Last Modified:||26 Dec 2012 08:49|
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