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Brachyury and Related Tbx Proteins Interact with the Mixl1 Homeodomain Protein and Negatively Regulate Mixl1 Transcriptional Activity

Mixl1 is a homeodomain transcription factor required for mesoderm and endoderm patterning during mammalian embryogenesis. Despite its crucial function in development, co-factors that modulate the activity of Mixl1 remain poorly defined. Here we report that Mixl1 interacts physically and functionally...

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Autores principales: Pereira, Lloyd A., Wong, Michael S., Lim, Sue Mei, Sides, Alexandra, Stanley, Edouard G., Elefanty, Andrew G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229578/
https://www.ncbi.nlm.nih.gov/pubmed/22164283
http://dx.doi.org/10.1371/journal.pone.0028394
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author Pereira, Lloyd A.
Wong, Michael S.
Lim, Sue Mei
Sides, Alexandra
Stanley, Edouard G.
Elefanty, Andrew G.
author_facet Pereira, Lloyd A.
Wong, Michael S.
Lim, Sue Mei
Sides, Alexandra
Stanley, Edouard G.
Elefanty, Andrew G.
author_sort Pereira, Lloyd A.
collection PubMed
description Mixl1 is a homeodomain transcription factor required for mesoderm and endoderm patterning during mammalian embryogenesis. Despite its crucial function in development, co-factors that modulate the activity of Mixl1 remain poorly defined. Here we report that Mixl1 interacts physically and functionally with the T-box protein Brachyury and related members of the T-box family of transcription factors. Transcriptional and protein analyses demonstrated overlapping expression of Mixl1 and Brachyury during embryonic stem cell differentiation. In vitro protein interaction studies showed that the Mixl1 with Brachyury associated via their DNA-binding domains and gel shift assays revealed that the Brachyury T-box domain bound to Mixl1-DNA complexes. Furthermore, luciferase reporter experiments indicated that association of Mixl1 with Brachyury and related T-box factors inhibited the transactivating potential of Mixl1 on the Gsc and Pdgfrα promoters. Our results indicate that the activity of Mixl1 can be modulated by protein-protein interactions and that T-box factors can function as negative regulators of Mixl1 activity.
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spelling pubmed-32295782011-12-07 Brachyury and Related Tbx Proteins Interact with the Mixl1 Homeodomain Protein and Negatively Regulate Mixl1 Transcriptional Activity Pereira, Lloyd A. Wong, Michael S. Lim, Sue Mei Sides, Alexandra Stanley, Edouard G. Elefanty, Andrew G. PLoS One Research Article Mixl1 is a homeodomain transcription factor required for mesoderm and endoderm patterning during mammalian embryogenesis. Despite its crucial function in development, co-factors that modulate the activity of Mixl1 remain poorly defined. Here we report that Mixl1 interacts physically and functionally with the T-box protein Brachyury and related members of the T-box family of transcription factors. Transcriptional and protein analyses demonstrated overlapping expression of Mixl1 and Brachyury during embryonic stem cell differentiation. In vitro protein interaction studies showed that the Mixl1 with Brachyury associated via their DNA-binding domains and gel shift assays revealed that the Brachyury T-box domain bound to Mixl1-DNA complexes. Furthermore, luciferase reporter experiments indicated that association of Mixl1 with Brachyury and related T-box factors inhibited the transactivating potential of Mixl1 on the Gsc and Pdgfrα promoters. Our results indicate that the activity of Mixl1 can be modulated by protein-protein interactions and that T-box factors can function as negative regulators of Mixl1 activity. Public Library of Science 2011-12-02 /pmc/articles/PMC3229578/ /pubmed/22164283 http://dx.doi.org/10.1371/journal.pone.0028394 Text en Pereira et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Pereira, Lloyd A.
Wong, Michael S.
Lim, Sue Mei
Sides, Alexandra
Stanley, Edouard G.
Elefanty, Andrew G.
Brachyury and Related Tbx Proteins Interact with the Mixl1 Homeodomain Protein and Negatively Regulate Mixl1 Transcriptional Activity
title Brachyury and Related Tbx Proteins Interact with the Mixl1 Homeodomain Protein and Negatively Regulate Mixl1 Transcriptional Activity
title_full Brachyury and Related Tbx Proteins Interact with the Mixl1 Homeodomain Protein and Negatively Regulate Mixl1 Transcriptional Activity
title_fullStr Brachyury and Related Tbx Proteins Interact with the Mixl1 Homeodomain Protein and Negatively Regulate Mixl1 Transcriptional Activity
title_full_unstemmed Brachyury and Related Tbx Proteins Interact with the Mixl1 Homeodomain Protein and Negatively Regulate Mixl1 Transcriptional Activity
title_short Brachyury and Related Tbx Proteins Interact with the Mixl1 Homeodomain Protein and Negatively Regulate Mixl1 Transcriptional Activity
title_sort brachyury and related tbx proteins interact with the mixl1 homeodomain protein and negatively regulate mixl1 transcriptional activity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229578/
https://www.ncbi.nlm.nih.gov/pubmed/22164283
http://dx.doi.org/10.1371/journal.pone.0028394
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