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Localization of the Domains in Runx Transcription Factors Required for the Repression of CD4 in Thymocytes

Telfer, J. C. and Hedblom, E. E. and Anderson, M. K. and Laurent, M. N. and Rothenberg, E. V. (2004) Localization of the Domains in Runx Transcription Factors Required for the Repression of CD4 in Thymocytes. Journal of Immunology, 172 (7). pp. 4359-4370. ISSN 0022-1767. doi:10.4049/jimmunol.172.7.4359. https://resolver.caltech.edu/CaltechAUTHORS:20170215-074451553

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Abstract

The runt family transcription factors Runx1 and Runx3 are expressed in developing murine thymocytes. We show that enforced expression of full-length Runx1 in CD4−CD8− thymocytes results in a profound suppression of immature CD4/CD8 double-positive thymocytes and mature CD4 single-positive thymocytes compared with controls. This effect arises from Runx1- or Runx3-mediated repression of CD4 expression, and is independent of positively selecting signals. Runx1 is able to repress CD4 in CD4/CD8 double-positive thymocytes, but not in mature splenic T cells. Runx-mediated CD4 repression is independent of association with the corepressors Groucho/TLE or Sin3. Two domains are required for complete Runx-mediated CD4 repression. These are contained within Runx1 aa 212–262 and 263–360. The latter region contains the nuclear matrix targeting sequence, which is highly conserved among runt family transcription factors across species. The presence of the nuclear matrix targeting sequence is required for Runx-mediated CD4 repression, suggesting that Runx transcription factors are stabilized on the CD4 silencer via association with the nuclear matrix.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.4049/jimmunol.172.7.4359DOIArticle
http://www.jimmunol.org/content/172/7/4359PublisherArticle
ORCID:
AuthorORCID
Rothenberg, E. V.0000-0002-3901-347X
Additional Information:© 2004 The American Association of Immunologists, Inc. Received for publication September 12, 2003. Accepted for publication January 20, 2004. This work was supported by National Science Foundation Grant MCB-9983129 and the DNA Sequencer Royalty Fund (to E.V.R.), and laboratory start up funds from the University of Massachusetts Amherst and Grant IRG 93-0333 from the American Cancer Society (to J.C.T.). We thank Dr. R. Pant for her help in cloning the skate Runx3 cDNA.
Funders:
Funding AgencyGrant Number
NSFMCB-9983129
University of Massachusetts AmherstUNSPECIFIED
DNA Sequencer Royalty Fund, CaltechUNSPECIFIED
American Cancer SocietyIRG 93-0333
Issue or Number:7
DOI:10.4049/jimmunol.172.7.4359
Record Number:CaltechAUTHORS:20170215-074451553
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170215-074451553
Official Citation:Localization of the Domains in Runx Transcription Factors Required for the Repression of CD4 in Thymocytes Janice C. Telfer, Emmett E. Hedblom, Michele K. Anderson, Micheline N. Laurent, Ellen V. Rothenberg The Journal of Immunology April 1, 2004, 172 (7) 4359-4370; DOI: 10.4049/jimmunol.172.7.4359
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74312
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:15 Feb 2017 17:14
Last Modified:11 Nov 2021 05:26

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