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Regulatory anatomy of the murine interleukin-2 gene

Novak, Thomas J. and White, Patricia M. and Rothenberg, Ellen V. (1990) Regulatory anatomy of the murine interleukin-2 gene. Nucleic Acids Research, 18 (15). pp. 4523-4533. ISSN 0305-1048. PMCID PMC331273. https://resolver.caltech.edu/CaltechAUTHORS:20170215-103934244

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Abstract

We have cloned the mouse IL2 gene and sequenced 2800 bp of 5′ flanking DNA. Comparison to the previously reported human sequence revealed extensive identity (−86%) between the two genes from +1 to − 580 with additional small islands of homology further upstream. Proximal sites which have been shown to be important in regulation of the human IL2 gene are well conserved in sequence and location. Transfection experiments using hybrid gene constructs containing varying lengths of the mouse 5′ flanking DNA linked to a CAT reporter gene have demonstrated the presence of several novel positive and negative regulatory elements. One negative regulatory region lying between −750 and −1000 consists primarily of alternating purines and pyrimidines and is absent from the human gene. The conserved region from − 321 and -578, an upstream segment from −1219 to −1332, and another region of −450 bp from −1449 to −1890, which contained a well-conserved sequence of 60 bp, were each associated with enhanced levels of expression. We found no evidence for intragenic or downstream enhancer elements in this gene. All the elements identified affect only the magnitude of the inducible response, for no region when deleted had the effect of altering either the need for induction, the kinetics of stimulation, or the cell-type specificity of expression. Deletion studies suggest a strong requirement for NFAT binding even in the presence of extensive 5′ flanking sequence. Therefore we conclude that IL2 gene expression is controlled primarily through a central T_H1-specific signaling pathway, which acts through proximal elements, while distal cis-elements exert a secondary modulating effect.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1093/nar/18.15.4523DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC331273/PubMed CentralArticle
ORCID:
AuthorORCID
Rothenberg, Ellen V.0000-0002-3901-347X
Additional Information:© 1990 Oxford University Press. Creative Commons Attribution Non-Commercial licence (CC BY-NC). Received: 04 April 1990; Revision Received: 11 June 1990; Accepted: 11 June 1990; Published: 11 August 1990. The authors would like to thank David Anderson, Frank Calzone, Eric Davidson, Paul Steinberg, and Barbara Wold for their helpful comments and advice. This work was submitted in partial fulfillment of the requirements for the Ph.D. degree at the California Institute of Technology. T.J.N. was supported in part by a predoctoral training grant from the USPHS. Research support was provided by USPHS grant CA39605 to E.V.R. Cathy Blagg and Vicki Hester provided excellent help preparing the manuscript.
Funders:
Funding AgencyGrant Number
NIHCA39605
NIH Predoctoral FellowshipUNSPECIFIED
Issue or Number:15
PubMed Central ID:PMC331273
Record Number:CaltechAUTHORS:20170215-103934244
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170215-103934244
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74320
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:15 Feb 2017 19:22
Last Modified:03 Oct 2019 16:37

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