Cargando…
Carboxy terminus of GATA4 transcription factor is required for its cardiogenic activity and interaction with CDK4
GATA4-6 transcription factors regulate numerous aspects of development and homeostasis in multiple tissues of mesodermal and endodermal origin. In the heart, the best studied of these factors, GATA4, has multiple distinct roles in cardiac specification, differentiation, morphogenesis, hypertrophy an...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259525/ https://www.ncbi.nlm.nih.gov/pubmed/25241353 http://dx.doi.org/10.1016/j.mod.2014.09.001 |
_version_ | 1782348035504734208 |
---|---|
author | Gallagher, Joseph M. Yamak, Abir Kirilenko, Pavel Black, Sarah Bochtler, Matthias Lefebvre, Chantal Nemer, Mona Latinkić, Branko V. |
author_facet | Gallagher, Joseph M. Yamak, Abir Kirilenko, Pavel Black, Sarah Bochtler, Matthias Lefebvre, Chantal Nemer, Mona Latinkić, Branko V. |
author_sort | Gallagher, Joseph M. |
collection | PubMed |
description | GATA4-6 transcription factors regulate numerous aspects of development and homeostasis in multiple tissues of mesodermal and endodermal origin. In the heart, the best studied of these factors, GATA4, has multiple distinct roles in cardiac specification, differentiation, morphogenesis, hypertrophy and survival. To improve understanding of how GATA4 achieves its numerous roles in the heart, here we have focused on the carboxy-terminal domain and the residues required for interaction with cofactors FOG2 and Tbx5. We present evidence that the carboxy terminal region composed of amino acids 362–400 is essential for mediating cardiogenesis in Xenopus pluripotent explants and embryos. In contrast, the same region is not required for endoderm-inducing activity of GATA4. Further evidence is presented that the carboxy terminal cardiogenic region of GATA4 does not operate as a generic transcriptional activator. Potential mechanism of action of the carboxy terminal end of GATA4 is provided by the results showing physical and functional interaction with CDK4, including the enhancement of cardiogenic activity of GATA4 by CDK4. These results establish CDK4 as a GATA4 partner in cardiogenesis. The interactions of GATA4 with its other well described cofactors Tbx5 and FOG2 are known to be involved in heart morphogenesis, but their requirement for cardiac differentiation is unknown. We report that the mutations that disrupt interactions of GATA4 with Tbx5 and FOG2, G295S and V217G, respectively, do not impair cardiogenic activity of GATA4. These findings add support to the view that distinct roles of GATA4 in the heart are mediated by different determinants of the protein. Finally, we show that the rat GATA4 likely induces cardiogenesis cell autonomously or directly as it does not require activity of endodermal transcription factor Sox17, a GATA4 target gene that induces cardiogenesis non-cell autonomously. |
format | Online Article Text |
id | pubmed-4259525 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-42595252014-12-09 Carboxy terminus of GATA4 transcription factor is required for its cardiogenic activity and interaction with CDK4 Gallagher, Joseph M. Yamak, Abir Kirilenko, Pavel Black, Sarah Bochtler, Matthias Lefebvre, Chantal Nemer, Mona Latinkić, Branko V. Mech Dev Article GATA4-6 transcription factors regulate numerous aspects of development and homeostasis in multiple tissues of mesodermal and endodermal origin. In the heart, the best studied of these factors, GATA4, has multiple distinct roles in cardiac specification, differentiation, morphogenesis, hypertrophy and survival. To improve understanding of how GATA4 achieves its numerous roles in the heart, here we have focused on the carboxy-terminal domain and the residues required for interaction with cofactors FOG2 and Tbx5. We present evidence that the carboxy terminal region composed of amino acids 362–400 is essential for mediating cardiogenesis in Xenopus pluripotent explants and embryos. In contrast, the same region is not required for endoderm-inducing activity of GATA4. Further evidence is presented that the carboxy terminal cardiogenic region of GATA4 does not operate as a generic transcriptional activator. Potential mechanism of action of the carboxy terminal end of GATA4 is provided by the results showing physical and functional interaction with CDK4, including the enhancement of cardiogenic activity of GATA4 by CDK4. These results establish CDK4 as a GATA4 partner in cardiogenesis. The interactions of GATA4 with its other well described cofactors Tbx5 and FOG2 are known to be involved in heart morphogenesis, but their requirement for cardiac differentiation is unknown. We report that the mutations that disrupt interactions of GATA4 with Tbx5 and FOG2, G295S and V217G, respectively, do not impair cardiogenic activity of GATA4. These findings add support to the view that distinct roles of GATA4 in the heart are mediated by different determinants of the protein. Finally, we show that the rat GATA4 likely induces cardiogenesis cell autonomously or directly as it does not require activity of endodermal transcription factor Sox17, a GATA4 target gene that induces cardiogenesis non-cell autonomously. Elsevier 2014-11 /pmc/articles/PMC4259525/ /pubmed/25241353 http://dx.doi.org/10.1016/j.mod.2014.09.001 Text en © 2014 The Authors https://creativecommons.org/licenses/by/3.0/This work is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/) . |
spellingShingle | Article Gallagher, Joseph M. Yamak, Abir Kirilenko, Pavel Black, Sarah Bochtler, Matthias Lefebvre, Chantal Nemer, Mona Latinkić, Branko V. Carboxy terminus of GATA4 transcription factor is required for its cardiogenic activity and interaction with CDK4 |
title | Carboxy terminus of GATA4 transcription factor is required for its cardiogenic activity and interaction with CDK4 |
title_full | Carboxy terminus of GATA4 transcription factor is required for its cardiogenic activity and interaction with CDK4 |
title_fullStr | Carboxy terminus of GATA4 transcription factor is required for its cardiogenic activity and interaction with CDK4 |
title_full_unstemmed | Carboxy terminus of GATA4 transcription factor is required for its cardiogenic activity and interaction with CDK4 |
title_short | Carboxy terminus of GATA4 transcription factor is required for its cardiogenic activity and interaction with CDK4 |
title_sort | carboxy terminus of gata4 transcription factor is required for its cardiogenic activity and interaction with cdk4 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259525/ https://www.ncbi.nlm.nih.gov/pubmed/25241353 http://dx.doi.org/10.1016/j.mod.2014.09.001 |
work_keys_str_mv | AT gallagherjosephm carboxyterminusofgata4transcriptionfactorisrequiredforitscardiogenicactivityandinteractionwithcdk4 AT yamakabir carboxyterminusofgata4transcriptionfactorisrequiredforitscardiogenicactivityandinteractionwithcdk4 AT kirilenkopavel carboxyterminusofgata4transcriptionfactorisrequiredforitscardiogenicactivityandinteractionwithcdk4 AT blacksarah carboxyterminusofgata4transcriptionfactorisrequiredforitscardiogenicactivityandinteractionwithcdk4 AT bochtlermatthias carboxyterminusofgata4transcriptionfactorisrequiredforitscardiogenicactivityandinteractionwithcdk4 AT lefebvrechantal carboxyterminusofgata4transcriptionfactorisrequiredforitscardiogenicactivityandinteractionwithcdk4 AT nemermona carboxyterminusofgata4transcriptionfactorisrequiredforitscardiogenicactivityandinteractionwithcdk4 AT latinkicbrankov carboxyterminusofgata4transcriptionfactorisrequiredforitscardiogenicactivityandinteractionwithcdk4 |