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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...

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Autores principales: Shao, Hui, Kono, Dwight H., Chen, Ling-Yu, Rubin, Elyssa M., Kaye, Jonathan
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1997
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.
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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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