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

   

Authors:	Martin-Malpartida, P.; Batet, M.; Kaczmarska, Z.; Freier, R.; Gomes, T.; Aragón, E.; Zou, Y.; Wang, Q.; Xi, Q.; Ruiz, L.; Vea, A.; Márquez, J. A.; Massagué, J.; Macias, M. J.
Article Title:	Structural basis for genome wide recognition of 5-bp GC motifs by SMAD transcription factors
Abstract:	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. © 2017 The Author(s).
Keywords:	controlled study; promoter region; nonhuman; animal cell; chromosome 12; mouse; gene; smad3 protein; transforming growth factor beta; embryo; protein; cytogenetics; dna; double stranded dna; molecular recognition; binding site; genome; dna sequence; hydrogen bond; immunoassay; dna binding; complementary dna; enhancer region; hydrogen; consensus sequence; smad4 protein; dna strand; isothermal titration calorimetry; cells and cell components; human; article; dna base composition
Journal Title:	Nature Communications
Volume:	8
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Date Published:	2017-12-12
Start Page:	2070
Language:	English
DOI:	10.1038/s41467-017-02054-6
PROVIDER:	scopus
PMCID:	PMC5727232
PUBMED:	29234012
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85037722974&doi=10.1038%2fs41467-017-02054-6&partnerID=40&md5=01e0bee2764d9b78a5011d171eda7f48
Notes:	Article -- Export Date: 2 January 2018 -- Source: Scopus

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