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Structural basis for genome wide recognition of 5-bp GC motifs by SMAD transcription factors

Smad transcription factors activated by TGF-β or by BMP receptors form trimeric complexes with Smad4 to target specific genes for cell fate regulation. The CAGAC motif has been considered as the main binding element for Smad2/3/4, whereas Smad1/5/8 have been thought to preferentially bind GC-rich el...

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Autores principales: Martin-Malpartida, Pau, Batet, Marta, Kaczmarska, Zuzanna, Freier, Regina, Gomes, Tiago, Aragón, Eric, Zou, Yilong, Wang, Qiong, Xi, Qiaoran, Ruiz, Lidia, Vea, Angela, Márquez, José A., Massagué, Joan, Macias, Maria J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727232/
https://www.ncbi.nlm.nih.gov/pubmed/29234012
http://dx.doi.org/10.1038/s41467-017-02054-6
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author Martin-Malpartida, Pau
Batet, Marta
Kaczmarska, Zuzanna
Freier, Regina
Gomes, Tiago
Aragón, Eric
Zou, Yilong
Wang, Qiong
Xi, Qiaoran
Ruiz, Lidia
Vea, Angela
Márquez, José A.
Massagué, Joan
Macias, Maria J.
author_facet Martin-Malpartida, Pau
Batet, Marta
Kaczmarska, Zuzanna
Freier, Regina
Gomes, Tiago
Aragón, Eric
Zou, Yilong
Wang, Qiong
Xi, Qiaoran
Ruiz, Lidia
Vea, Angela
Márquez, José A.
Massagué, Joan
Macias, Maria J.
author_sort Martin-Malpartida, Pau
collection PubMed
description Smad transcription factors activated by TGF-β or by BMP receptors form trimeric complexes with Smad4 to target specific genes for cell fate regulation. The CAGAC motif has been considered as the main binding element for Smad2/3/4, whereas Smad1/5/8 have been thought to preferentially bind GC-rich elements. However, chromatin immunoprecipitation analysis in embryonic stem cells showed extensive binding of Smad2/3/4 to GC-rich cis-regulatory elements. Here, we present the structural basis for specific binding of Smad3 and Smad4 to GC-rich motifs in the goosecoid promoter, a nodal-regulated differentiation gene. The structures revealed a 5-bp consensus sequence GGC(GC)|(CG) as the binding site for both TGF-β and BMP-activated Smads and for Smad4. These 5GC motifs are highly represented as clusters in Smad-bound regions genome-wide. Our results provide a basis for understanding the functional adaptability of Smads in different cellular contexts, and their dependence on lineage-determining transcription factors to target specific genes in TGF-β and BMP pathways.
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spelling pubmed-57272322017-12-14 Structural basis for genome wide recognition of 5-bp GC motifs by SMAD transcription factors Martin-Malpartida, Pau Batet, Marta Kaczmarska, Zuzanna Freier, Regina Gomes, Tiago Aragón, Eric Zou, Yilong Wang, Qiong Xi, Qiaoran Ruiz, Lidia Vea, Angela Márquez, José A. Massagué, Joan Macias, Maria J. Nat Commun Article Smad transcription factors activated by TGF-β or by BMP receptors form trimeric complexes with Smad4 to target specific genes for cell fate regulation. The CAGAC motif has been considered as the main binding element for Smad2/3/4, whereas Smad1/5/8 have been thought to preferentially bind GC-rich elements. However, chromatin immunoprecipitation analysis in embryonic stem cells showed extensive binding of Smad2/3/4 to GC-rich cis-regulatory elements. Here, we present the structural basis for specific binding of Smad3 and Smad4 to GC-rich motifs in the goosecoid promoter, a nodal-regulated differentiation gene. The structures revealed a 5-bp consensus sequence GGC(GC)|(CG) as the binding site for both TGF-β and BMP-activated Smads and for Smad4. These 5GC motifs are highly represented as clusters in Smad-bound regions genome-wide. Our results provide a basis for understanding the functional adaptability of Smads in different cellular contexts, and their dependence on lineage-determining transcription factors to target specific genes in TGF-β and BMP pathways. Nature Publishing Group UK 2017-12-12 /pmc/articles/PMC5727232/ /pubmed/29234012 http://dx.doi.org/10.1038/s41467-017-02054-6 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Martin-Malpartida, Pau
Batet, Marta
Kaczmarska, Zuzanna
Freier, Regina
Gomes, Tiago
Aragón, Eric
Zou, Yilong
Wang, Qiong
Xi, Qiaoran
Ruiz, Lidia
Vea, Angela
Márquez, José A.
Massagué, Joan
Macias, Maria J.
Structural basis for genome wide recognition of 5-bp GC motifs by SMAD transcription factors
title Structural basis for genome wide recognition of 5-bp GC motifs by SMAD transcription factors
title_full Structural basis for genome wide recognition of 5-bp GC motifs by SMAD transcription factors
title_fullStr Structural basis for genome wide recognition of 5-bp GC motifs by SMAD transcription factors
title_full_unstemmed Structural basis for genome wide recognition of 5-bp GC motifs by SMAD transcription factors
title_short Structural basis for genome wide recognition of 5-bp GC motifs by SMAD transcription factors
title_sort structural basis for genome wide recognition of 5-bp gc motifs by smad transcription factors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727232/
https://www.ncbi.nlm.nih.gov/pubmed/29234012
http://dx.doi.org/10.1038/s41467-017-02054-6
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