The NF-YB/NF-YC Structure Gives Insight into DNA Binding and Transcription Regulation by CCAAT Factor NF-Y

Abstract

The heterotrimeric transcription factor NF-Y recognizes with high specificity and affinity the CCAAT regulatory element that is widely represented in promoters and enhancer regions. The CCAAT box acts in concert with neighboring elements, and its bending by NF-Y is thought to be a major mechanism required for transcription activation. We have solved the structure of the NF-YC/NF-YB subcomplex of NF-Y, which shows that the core domains of both proteins interact through histone fold motifs. This histone-like pair is closely related to the H2A/H2B and NC2␣/NC2␤ families, with features that are both common to this class of proteins and unique to NF-Y. The structure together with the modeling of the nonspecific interaction of NF-YC/NF-YB with DNA and the full NF-Y/CCAAT box complex highlight important structural features that account for different and possibly similar biological functions of the transcriptional regulators NF-Y and NC2. In particular, it emphasizes the role of the newly described ␣C helix of NF-YC, which is both important for NF-Y trimerization and a target for regulatory proteins, such as MYC and p53.

Cap2-HAP Complex Is a Critical Transcriptional Regulator That Has Dual but Contrasting Roles in Regulation of Iron Homeostasis in Candida albicans

“…9). Structural studies using mammalian NF-YB and NF-YC heterodimers, the orthologs of Hap3 and Hap5 proteins, respectively, showed that their interaction occurred through histone H2A/H2B-like histone-fold domains (81). Moreover, the Hap32 and Hap5 proteins also could heterodimerize through their histone-fold domains (as reviewed in Ref.…”

The Short Isoform of NF‐YA Belongs to the Embryonic Stem Cell Transcription Factor Circuitry

“…The CCAAT box is recognized with high affinity and specificity by NF-Y, a heterotrimer composed of NF-YA, NF-YB, and NF-YC, all evolutionarily conserved [12]. NF-YB and NF-YC contain histone fold domains (HFD), structurally related to histones H2B and H2A, and forming a stable histone-like dimer [12]. NF-YA associates to the HFD dimer, conferring CCAAT specificity to the complex.…”

“…Although the CCAAT was found in some enhancers before [9,10], it has been mainly considered as a promoter element: it is positioned between À60 and À100 with respect to the transcriptional start site, and the importance is underscored by mutations causing a drop, or complete elimination, of promoter activity [11]. The CCAAT box is recognized with high affinity and specificity by NF-Y, a heterotrimer composed of NF-YA, NF-YB, and NF-YC, all evolutionarily conserved [12]. NF-YB and NF-YC contain histone fold domains (HFD), structurally related to histones H2B and H2A, and forming a stable histone-like dimer [12].…”

NF-YC Functions as a Corepressor of Agonist-bound Mineralocorticoid Receptor

“…Each subunit has a core region, which has been conserved throughout evolution. The conserved regions of the two subunits NF-YB and NF-YC contain histone fold motifs, which are required for the heterodimerization as a prerequisite for NF-YA association and CCAAT binding (18,34,35). The presence of histone fold motifs in the NF-YB and NF-YC implicates these proteins as being likely to have multiple protein-protein interactions with other transcription factors as well as being given protein modifications.…”