GATA-1 interacts with the myeloid PU.1 transcription factor and represses PU.1-dependent transcription.

The GATA-1 transcription factor is capable of suppressing the myeloid gene expression program when ectopically expressed in myeloid cells. We examined the ability of GATA-1 to repress the expression and function of the PU.1 transcription factor, a central regulator of myeloid differentiation. We fou...

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Main Authors: Nerlov, C, Querfurth, E, Kulessa, H, Graf, T
Formato: Journal article
Idioma:English
Publicado: 2000
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author Nerlov, C
Querfurth, E
Kulessa, H
Graf, T
author_facet Nerlov, C
Querfurth, E
Kulessa, H
Graf, T
author_sort Nerlov, C
collection OXFORD
description The GATA-1 transcription factor is capable of suppressing the myeloid gene expression program when ectopically expressed in myeloid cells. We examined the ability of GATA-1 to repress the expression and function of the PU.1 transcription factor, a central regulator of myeloid differentiation. We found that GATA-1 is capable of suppressing the myeloid phenotype without interfering with PU.1 gene expression, but instead was capable of inhibiting the activity of the PU.1 protein in a dose-dependent manner. This inhibition was independent of the ability of GATA-1 to bind DNA, suggesting that it is mediated by protein-protein interaction. We examined the ability of PU.1 to interact with GATA-1 and found a direct interaction between the PU.1 ETS domain and the C-terminal finger region of GATA-1. Replacing the PU.1 ETS domain with the GAL4 DNA-binding domain removed the ability of GATA-1 to inhibit PU.1 activity, indicating that the PU.1 DNA-binding domain, rather than the transactivation domain, is the target for GATA-1-mediated repression. We therefore propose that GATA-1 represses myeloid gene expression, at least in part, through its ability to directly interact with the PU.1 ETS domain and thereby interfere with PU.1 function. (Blood. 2000;95:2543-2551)
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spelling oxford-uuid:f9e5e5d1-fea5-47d3-868a-1abd7cc471412022-03-27T13:01:31ZGATA-1 interacts with the myeloid PU.1 transcription factor and represses PU.1-dependent transcription.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f9e5e5d1-fea5-47d3-868a-1abd7cc47141EnglishSymplectic Elements at Oxford2000Nerlov, CQuerfurth, EKulessa, HGraf, TThe GATA-1 transcription factor is capable of suppressing the myeloid gene expression program when ectopically expressed in myeloid cells. We examined the ability of GATA-1 to repress the expression and function of the PU.1 transcription factor, a central regulator of myeloid differentiation. We found that GATA-1 is capable of suppressing the myeloid phenotype without interfering with PU.1 gene expression, but instead was capable of inhibiting the activity of the PU.1 protein in a dose-dependent manner. This inhibition was independent of the ability of GATA-1 to bind DNA, suggesting that it is mediated by protein-protein interaction. We examined the ability of PU.1 to interact with GATA-1 and found a direct interaction between the PU.1 ETS domain and the C-terminal finger region of GATA-1. Replacing the PU.1 ETS domain with the GAL4 DNA-binding domain removed the ability of GATA-1 to inhibit PU.1 activity, indicating that the PU.1 DNA-binding domain, rather than the transactivation domain, is the target for GATA-1-mediated repression. We therefore propose that GATA-1 represses myeloid gene expression, at least in part, through its ability to directly interact with the PU.1 ETS domain and thereby interfere with PU.1 function. (Blood. 2000;95:2543-2551)
spellingShingle Nerlov, C
Querfurth, E
Kulessa, H
Graf, T
GATA-1 interacts with the myeloid PU.1 transcription factor and represses PU.1-dependent transcription.
title GATA-1 interacts with the myeloid PU.1 transcription factor and represses PU.1-dependent transcription.
title_full GATA-1 interacts with the myeloid PU.1 transcription factor and represses PU.1-dependent transcription.
title_fullStr GATA-1 interacts with the myeloid PU.1 transcription factor and represses PU.1-dependent transcription.
title_full_unstemmed GATA-1 interacts with the myeloid PU.1 transcription factor and represses PU.1-dependent transcription.
title_short GATA-1 interacts with the myeloid PU.1 transcription factor and represses PU.1-dependent transcription.
title_sort gata 1 interacts with the myeloid pu 1 transcription factor and represses pu 1 dependent transcription
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AT querfurthe gata1interactswiththemyeloidpu1transcriptionfactorandrepressespu1dependenttranscription
AT kulessah gata1interactswiththemyeloidpu1transcriptionfactorandrepressespu1dependenttranscription
AT graft gata1interactswiththemyeloidpu1transcriptionfactorandrepressespu1dependenttranscription