Structural determinants for NF-Y/DNA interaction at the CCAAT box.
The recently determined crystal structures of the sequence-specific transcription factor NF-Y have illuminated the structural mechanism underlying transcription at the CCAAT box. NF-Y is a trimeric protein complex composed by the NF-YA, NF-YB, and NF-YC subunits. NF-YB and NF-YC contain a histone-like domain and assemble on a head-to-tail fashion to form a dimer, which provides the structural scaffold for the DNA sugar-phosphate backbone binding (mimicking the nucleosome H2A/H2B-DNA assembly) and for the interaction with NF-YA. The NF-YA subunit hosts two structurally extended α-helices; one is involved in NF-YB/NF-YC binding and the other inserts deeply into the DNA minor groove, providing exquisite sequence-specificity for recognition and binding of the CCAAT box. The analysis of these structural data is expected to serve as a powerful guide for future experiments aimed at understanding the role of post-translational modification at NF-Y regulation sites and to unravel the three-dimensional architecture of higher order complexes formed between NF-Y and other transcription factors that act synergistically for transcription activation. Moreover, these structures represent an excellent starting point to challenge the formation of a stable hybrid nucleosome between NF-Y and core histone proteins, and to rationalize the fine molecular details associated with the wide combinatorial association of plant NF-Y subunits. This article is part of a Special Issue entitled: Nuclear Factor Y in Development and Disease, edited by Prof. Roberto Mantovani.
Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy.
Valentina
V
Nardone
Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy.
Antonio
A
Chaves-Sanjuan
Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy. Electronic address: marco.nardini@unimi.it.
Marco
M
Nardini
D000818:Animals; D023081:CCAAT-Binding Factor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D020218:Response Elements
D023081:CCAAT-Binding Factor; C492061:NFYA protein, human; C492063:NFYB protein, human; C469358:NFYC protein, human
DNA-binding; Histones; NF-Y; Transcription factor; X-ray crystallography