Structural basis for genome wide recognition of 5-bp GC motifs by SMAD transcription factors
Márquez, José A.
Macias, Maria J.Note: Order does not necessarily reflect citation order of authors.
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CitationMartin-Malpartida, P., M. Batet, Z. Kaczmarska, R. Freier, T. Gomes, E. Aragón, Y. Zou, et al. 2017. “Structural basis for genome wide recognition of 5-bp GC motifs by SMAD transcription factors.” Nature Communications 8 (1): 2070. doi:10.1038/s41467-017-02054-6. http://dx.doi.org/10.1038/s41467-017-02054-6.
AbstractSmad 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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