The sequence-specific transcription factor NF-Y binds the CCAAT box, one of the sequence elements most frequently found in eukaryotic promoters. NF-Y is composed of the NF-YA and NF-YB/NF-YC subunits, the latter two hosting histone-fold domains (HFDs). The crystal structure of NF-Y bound to a 25 bp CCAAT oligonucleotide shows that the HFD dimer binds to the DNA sugar-phosphate backbone, mimicking the nucleosome H2A/H2B-DNA assembly. NF-YA both binds to NF-YB/NF-YC and inserts an a helix deeply into the DNA minor groove, providing sequence-specific contacts to the CCAAT box. Structural considerations and mutational data indicate that NF-YB ubiquitination at Lys138 precedes and is equivalent to H2B Lys120 monoubiquitination, important in transcriptional activation. Thus, NF-Y is a sequence-specific transcription factor with nucleosome-like properties of nonspecific DNA binding and helps establish permissive chromatin modifications at CCAAT promoters. Our findings suggest that other HFD-containing proteins may function in similar ways.

Sequence-specific transcription factor NF-Y displays histone-like DNA binding and H2B-like ubiquitination

DONATI, Giacomo;
2013-01-01

Abstract

The sequence-specific transcription factor NF-Y binds the CCAAT box, one of the sequence elements most frequently found in eukaryotic promoters. NF-Y is composed of the NF-YA and NF-YB/NF-YC subunits, the latter two hosting histone-fold domains (HFDs). The crystal structure of NF-Y bound to a 25 bp CCAAT oligonucleotide shows that the HFD dimer binds to the DNA sugar-phosphate backbone, mimicking the nucleosome H2A/H2B-DNA assembly. NF-YA both binds to NF-YB/NF-YC and inserts an a helix deeply into the DNA minor groove, providing sequence-specific contacts to the CCAAT box. Structural considerations and mutational data indicate that NF-YB ubiquitination at Lys138 precedes and is equivalent to H2B Lys120 monoubiquitination, important in transcriptional activation. Thus, NF-Y is a sequence-specific transcription factor with nucleosome-like properties of nonspecific DNA binding and helps establish permissive chromatin modifications at CCAAT promoters. Our findings suggest that other HFD-containing proteins may function in similar ways.
2013
152
1-2
132
143
Amino Acid Sequence; Animals; CCAAT-Binding Factor; Crystallography, X-Ray; DNA; HSP72 Heat-Shock Proteins; Histones; Humans; Molecular Sequence Data; Multiprotein Complexes; Oligonucleotides; Promoter Regions, Genetic; Protein Structure, Tertiary; Sequence Alignment; Ubiquitination; Biochemistry, Genetics and Molecular Biology (all)
Nardini, Marco; Gnesutta, Nerina; Donati, Giacomo; Gatta, Raffaella; Forni, Claudia; Fossati, Andrea; Vonrhein, Clemens; Moras, Dino; Romier, Christophe; Bolognesi, Martino; Mantovani, Roberto
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1590740
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