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Induction of the Early Growth Response (Egr) Family of Transcription Factors during Thymic Selection
There is little known about the regulation of gene expression during TCR-mediated differentiation of immature CD4(+)8(+) (double positive) thymocytes into mature T cells. Using the DPK CD4(+)8(+)thymocyte precursor cell line, we demonstrate that the early growth response-1 gene (Erg-1), encoding a z...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
1997
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196139/ https://www.ncbi.nlm.nih.gov/pubmed/9034151 |
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author | Shao, Hui Kono, Dwight H. Chen, Ling-Yu Rubin, Elyssa M. Kaye, Jonathan |
author_facet | Shao, Hui Kono, Dwight H. Chen, Ling-Yu Rubin, Elyssa M. Kaye, Jonathan |
author_sort | Shao, Hui |
collection | PubMed |
description | There is little known about the regulation of gene expression during TCR-mediated differentiation of immature CD4(+)8(+) (double positive) thymocytes into mature T cells. Using the DPK CD4(+)8(+)thymocyte precursor cell line, we demonstrate that the early growth response-1 gene (Erg-1), encoding a zinc finger transcription factor, is rapidly upregulated after TCR stimulation. We also report that Egr-1 is expressed by a subset of normal double positive thymocytes in the thymic cortex, as well by a majority of medullary single positive thymocytes. Expression of Egr-1 is dramatically reduced in the thymus of major histocompatibility complex knockout mice, but can be induced by anti-CD3 antibody stimulation of isolated thymocytes from these animals. These and other data suggest that high level expression of Egr-1 in the thymus is a consequence of selection. A similar pattern of expression is found for family members Egr-2 and Egr-3. Using the DPK cell line, we also demonstrate that expression of Egr-1, 2, and 3 is dependent upon ras activation, as is the initiation of differentiation to a single positive cell. In contrast, the calcineurin inhibitor cyclosporin A, which inhibits DPK cell differentiation as well as positive selection, inhibits expression of Egr-2 and Egr-3, but not Egr-1. The identification of the Egr family in this context represents the first report of a link between the two known signaling pathways involved in positive selection and downstream transcriptional regulators. |
format | Text |
id | pubmed-2196139 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1997 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21961392008-04-16 Induction of the Early Growth Response (Egr) Family of Transcription Factors during Thymic Selection Shao, Hui Kono, Dwight H. Chen, Ling-Yu Rubin, Elyssa M. Kaye, Jonathan J Exp Med Article There is little known about the regulation of gene expression during TCR-mediated differentiation of immature CD4(+)8(+) (double positive) thymocytes into mature T cells. Using the DPK CD4(+)8(+)thymocyte precursor cell line, we demonstrate that the early growth response-1 gene (Erg-1), encoding a zinc finger transcription factor, is rapidly upregulated after TCR stimulation. We also report that Egr-1 is expressed by a subset of normal double positive thymocytes in the thymic cortex, as well by a majority of medullary single positive thymocytes. Expression of Egr-1 is dramatically reduced in the thymus of major histocompatibility complex knockout mice, but can be induced by anti-CD3 antibody stimulation of isolated thymocytes from these animals. These and other data suggest that high level expression of Egr-1 in the thymus is a consequence of selection. A similar pattern of expression is found for family members Egr-2 and Egr-3. Using the DPK cell line, we also demonstrate that expression of Egr-1, 2, and 3 is dependent upon ras activation, as is the initiation of differentiation to a single positive cell. In contrast, the calcineurin inhibitor cyclosporin A, which inhibits DPK cell differentiation as well as positive selection, inhibits expression of Egr-2 and Egr-3, but not Egr-1. The identification of the Egr family in this context represents the first report of a link between the two known signaling pathways involved in positive selection and downstream transcriptional regulators. The Rockefeller University Press 1997-02-17 /pmc/articles/PMC2196139/ /pubmed/9034151 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Shao, Hui Kono, Dwight H. Chen, Ling-Yu Rubin, Elyssa M. Kaye, Jonathan Induction of the Early Growth Response (Egr) Family of Transcription Factors during Thymic Selection |
title | Induction of the Early Growth Response (Egr) Family of Transcription Factors during Thymic Selection |
title_full | Induction of the Early Growth Response (Egr) Family of Transcription Factors during Thymic Selection |
title_fullStr | Induction of the Early Growth Response (Egr) Family of Transcription Factors during Thymic Selection |
title_full_unstemmed | Induction of the Early Growth Response (Egr) Family of Transcription Factors during Thymic Selection |
title_short | Induction of the Early Growth Response (Egr) Family of Transcription Factors during Thymic Selection |
title_sort | induction of the early growth response (egr) family of transcription factors during thymic selection |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196139/ https://www.ncbi.nlm.nih.gov/pubmed/9034151 |
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