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.

The USR domain of USF1 mediates NF-Y interactions and cooperative DNA binding / A. Bernardini, M. Lorenzo, A. Chaves Sanjuan, P. Swuec, M. Pigni, D. Saad, P.V. Konarev, M. Ann Graewert, E. Valentini, D.I. Svergun, M. Nardini, R. Mantovani, N.B. Gnesutta. - In: INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES. - ISSN 0141-8130. - 193:part a(2021 Dec 15), pp. 401-413. [10.1016/j.ijbiomac.2021.10.056]

The USR domain of USF1 mediates NF-Y interactions and cooperative DNA binding

A. Bernardini
Primo
;
M. Lorenzo
Secondo
;
A. Chaves Sanjuan;P. Swuec;D. Saad;M. Nardini;R. Mantovani
Penultimo
;
N.B. Gnesutta
Ultimo
2021-12-15

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.
trans-activation domain; SAXS; intrinsically disordered region; protein-DNA interactions; DNA-binding domain
Settore BIO/10 - Biochimica
Settore BIO/18 - Genetica
18-ott-2021
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/878487
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