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

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

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

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Citation: Martin-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.
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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.
Published Version: doi:10.1038/s41467-017-02054-6
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727232/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:34652059
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