1. The USR domain of USF1 mediates NF-Y interactions and cooperative DNA binding
- Author
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Dana Saad, Nerina Gnesutta, Erica Valentini, Roberto Mantovani, Antonio Chaves-Sanjuan, Melissa A. Graewert, Andrea Bernardini, Petr V. Konarev, Marco Nardini, Matteo Pigni, Paolo Swuec, Dmitri I. Svergun, and Mariangela Lorenzo
- Subjects
genetic structures ,biology ,Chemistry ,USF1 ,Colocalization ,Promoter ,DNA ,General Medicine ,DNA-binding domain ,Biochemistry ,Cell biology ,chemistry.chemical_compound ,Gene Expression Regulation ,Protein Domains ,Structural Biology ,Gene expression ,biology.protein ,Humans ,Upstream Stimulatory Factors ,Promoter Regions, Genetic ,Molecular Biology ,Peptide sequence ,Transcription factor ,Protein Binding - Abstract
The trimeric CCAAT-binding NF-Y is a “pioneer” Transcription Factor -TF- known to cooperate with neighboring TFs to regulate gene expression. Genome-wide analyses detected a precise stereo-alignment ‐10/12 bp- of CCAAT with E-box elements and corresponding colocalization of NF-Y with basic-Helix-Loop-Helix (bHLH) TFs. We dissected here NF-Y interactions with USF1 and MAX. USF1, but not MAX, cooperates in DNA binding with NF-Y. NF-Y and USF1 synergize to activate target promoters. Reconstruction of complexes by structural means shows independent DNA binding of MAX, whereas USF1 has extended contacts with NF-Y, involving the USR, a USF-specific amino acid sequence stretch required for trans-activation. The USR is an intrinsically disordered domain and adopts different conformations based on E-box–CCAAT distances. Deletion of the USR abolishes cooperative DNA binding with NF-Y. Our data indicate that the functionality of certain unstructured domains involves adapting to small variation in stereo-alignments of the multimeric TFs sites.
- Published
- 2021
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