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Expression of the Mouse Pre-T Cell Receptor α Gene Is Controlled by an Upstream Region Containing a Transcriptional Enhancer

The pre-T cell receptor α (pTα) protein is a critical component of the pre-T cell receptor complex in early thymocytes. The expression of the pTα gene is one of the earliest markers of the T cell lineage and occurs exclusively in pre-T cells. To investigate the molecular basis of thymocyte-specific...

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Detalles Bibliográficos
Autores principales: Reizis, Boris, Leder, Philip
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1999
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193641/
https://www.ncbi.nlm.nih.gov/pubmed/10330446
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author Reizis, Boris
Leder, Philip
author_facet Reizis, Boris
Leder, Philip
author_sort Reizis, Boris
collection PubMed
description The pre-T cell receptor α (pTα) protein is a critical component of the pre-T cell receptor complex in early thymocytes. The expression of the pTα gene is one of the earliest markers of the T cell lineage and occurs exclusively in pre-T cells. To investigate the molecular basis of thymocyte-specific gene expression, we searched for the genomic elements regulating transcription of the mouse pTα gene. We now report that expression of the pTα gene is primarily controlled by an upstream genomic region, which can drive thymocyte-specific expression of a marker gene in transgenic mice. Within this region, we have identified two specific DNase-hypersensitive sites corresponding to a proximal promoter and an upstream transcriptional enhancer. The pTα enhancer appears to function preferentially in pre-T cell lines and binds multiple nuclear factors, including YY1. The enhancer also contains two G-rich stretches homologous to a critical region of the thymocyte-specific lck proximal promoter. Here we show that these sites bind a common nuclear factor and identify it as the zinc finger protein ZBP-89. Our data establish a novel experimental model for thymocyte-specific gene expression and suggest an important role for ZBP-89 in T cell development.
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spelling pubmed-21936412008-04-16 Expression of the Mouse Pre-T Cell Receptor α Gene Is Controlled by an Upstream Region Containing a Transcriptional Enhancer Reizis, Boris Leder, Philip J Exp Med Articles The pre-T cell receptor α (pTα) protein is a critical component of the pre-T cell receptor complex in early thymocytes. The expression of the pTα gene is one of the earliest markers of the T cell lineage and occurs exclusively in pre-T cells. To investigate the molecular basis of thymocyte-specific gene expression, we searched for the genomic elements regulating transcription of the mouse pTα gene. We now report that expression of the pTα gene is primarily controlled by an upstream genomic region, which can drive thymocyte-specific expression of a marker gene in transgenic mice. Within this region, we have identified two specific DNase-hypersensitive sites corresponding to a proximal promoter and an upstream transcriptional enhancer. The pTα enhancer appears to function preferentially in pre-T cell lines and binds multiple nuclear factors, including YY1. The enhancer also contains two G-rich stretches homologous to a critical region of the thymocyte-specific lck proximal promoter. Here we show that these sites bind a common nuclear factor and identify it as the zinc finger protein ZBP-89. Our data establish a novel experimental model for thymocyte-specific gene expression and suggest an important role for ZBP-89 in T cell development. The Rockefeller University Press 1999-05-17 /pmc/articles/PMC2193641/ /pubmed/10330446 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 Articles
Reizis, Boris
Leder, Philip
Expression of the Mouse Pre-T Cell Receptor α Gene Is Controlled by an Upstream Region Containing a Transcriptional Enhancer
title Expression of the Mouse Pre-T Cell Receptor α Gene Is Controlled by an Upstream Region Containing a Transcriptional Enhancer
title_full Expression of the Mouse Pre-T Cell Receptor α Gene Is Controlled by an Upstream Region Containing a Transcriptional Enhancer
title_fullStr Expression of the Mouse Pre-T Cell Receptor α Gene Is Controlled by an Upstream Region Containing a Transcriptional Enhancer
title_full_unstemmed Expression of the Mouse Pre-T Cell Receptor α Gene Is Controlled by an Upstream Region Containing a Transcriptional Enhancer
title_short Expression of the Mouse Pre-T Cell Receptor α Gene Is Controlled by an Upstream Region Containing a Transcriptional Enhancer
title_sort expression of the mouse pre-t cell receptor α gene is controlled by an upstream region containing a transcriptional enhancer
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193641/
https://www.ncbi.nlm.nih.gov/pubmed/10330446
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