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Identification of a cell type-specific silencer in the first exon of the His-1 gene

Xu, Fan and Paquette, Alice J. and Anderson, David J. and Charalambous, Andreas and Askew, David S. (2000) Identification of a cell type-specific silencer in the first exon of the His-1 gene. Journal of Cellular Biochemistry, 76 (4). pp. 615-624. ISSN 0730-2312. http://resolver.caltech.edu/CaltechAUTHORS:20150312-132000071

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Abstract

The His-1 gene is developmentally expressed in the murine choroid plexus but is silenced in the adult brain. To test the hypothesis that the gene contains cis-acting elements that contribute to this repression, we have analyzed segments of the proximal promoter for negative regulatory sequences by transient transfection analysis. The activity of the proximal promoter was moderately influenced by positively and negatively acting sequences located from 2335 to 2168 and 2617 to 2335, respectively. A strong His-1-positive regulatory element (HPRE, 118 to 129) was essential for maximal promoter activity and could also enhance the activity of the heterologous SV40 promoter in an orientation-dependent manner. The HPRE contains homology to the neuronal restrictive silencer element (NRSE) but interacted with nuclear proteins that were distinct from the NRSE-binding factor (NRSF). By contrast, a potent negative regulatory sequence (HNRE) was identified in the first exon that repressed either the His-1 or SV40 promoters by greater than 80%. This negative regulatory sequence interacted with nuclear proteins from cells that contain a silent His-1 gene but showed no interaction with nuclear proteins from cells that actively transcribe the endogenous gene. HNRE-mediated repression was orientation independent; most of this activity was mapped to a minimal 26-bp sequence. These findings suggest that the first exon of the His-1 gene contains a cell type-specific silencer that contributes to the regulation of His-1 transcription.


Item Type:Article
Related URLs:
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http://dx.doi.org/10.1002/(SICI)1097-4644(20000315)76:4<615::AID-JCB10>3.0.CO;2-Y DOIArticle
http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-4644(20000315)76:4%3C615::AID-JCB10%3E3.0.CO;2-Y/abstractPublisherArticle
Additional Information:© 2000 Wiley-Liss, Inc. Received 21 July 1999; Accepted 2 September 1999. First published: 31 January 2000. We thank Molly McFarland for excellent technical assistance and Dr. Phil Howles for critical review of the manuscript. These studies were supported by National Institutes of Health grant CA61909 and by an American Cancer Society Junior Faculty Research Award (to D.S.A.), National Institutes of Health grant NS23476 (to D.J.A.), and a National Institutes of Health predoctoral training grant (to A.J.P.).
Funders:
Funding AgencyGrant Number
NIHCA61909
American Cancer Society Junior Faculty Research AwardUNSPECIFIED
NIHNS23476
NIH Predoctoral Training GrantUNSPECIFIED
Subject Keywords:oncogene; HIS-1; promoter; silencer; gene regulation; choroid plexus
Record Number:CaltechAUTHORS:20150312-132000071
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20150312-132000071
Official Citation:Xu, F., Paquette, A. J., Anderson, D. J., Charalambous, A. and Askew, D. S. (2000), Identification of a cell type-specific silencer in the first exon of the His-1 gene. J. Cell. Biochem., 76: 615–624. doi:10.1002/(SICI)1097-4644(20000315)76:4<615::AID-JCB10>3.0.CO;2-Y
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:55736
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:12 Mar 2015 21:40
Last Modified:12 Mar 2015 21:40

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