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Carboxy terminus of GATA4 transcription factor is required for its cardiogenic activity and interaction with CDK4.

Object's details: Carboxy terminus of GATA4 transcription factor is required for its cardiogenic activity and interaction with CDK4.

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Provider:Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk

Description

Title:
Carboxy terminus of GATA4 transcription factor is required for its cardiogenic activity and interaction with CDK4.
Creator:
Gallagher, Joseph M.;
Yamak, Abir;
Kirilenko, Pavel;
Black, Sarah;
Bochtler, Matthias;
Lefebvre, Chantal;
Nemer, Mona;
Latinkić, Branko V.
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.
Object availability:
free access
Date:
2014.11
Type:
Article;
PeerReviewed
Language:
English
Format:
application/pdf
Publisher:
Elsevier Ireland Ltd.
Relation: http://eprints.ibb.waw.pl/885 ;http://sciencedirect.com/science/journal/09254773 ;doi:10.1016/j.mod.2014.09.001
Subject:
R Medicine (General)
Identifier: http://eprints.ibb.waw.pl/885/2/2014_GATA4_Bochtler_Latinkic.pdf ;
Gallagher, Joseph M. and Yamak, Abir and Kirilenko, Pavel and Black, Sarah and Bochtler, Matthias and Lefebvre, Chantal and Nemer, Mona and Latinkić, Branko V. (2014) Carboxy terminus of GATA4 transcription factor is required for its cardiogenic activity and interaction with CDK4. Mechanisms of Development, 134 . pp. 31-41. ISSN 0925-4773
Data provider:
Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk

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