Nuclear factor-Y (NF-Y) is a class of transcription factor (TF) that plays decisive roles in diverse developmental pathways in plants and other eukaryotes. These are also present in other eukaryotes as known as CCAAT-binding factor (CBF) or heme activator protein (HAP).  NF-Y specifically recognizes the regulatory CCAAT element found in either orientation in the proximal and distal enhancer regions of many genes. In higher eukaryotes, this element is found in about 30% of the promoters, preferentially in the −60/−100 region. 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.

NF-Y is a heterotrimeric complex composed of NF-YA (CBF-B,HAP2), NF-YB (CBF-A, HAP3), and NF-YC (CBF-C, HAP5) which are all required for CCAAT binding. Within the NF-Y family, two groups of proteins, Down-regulator Dr1 (NC2β) and Down-regulator associated protein Drap1 (NC2α) act as negative cofactors and are related to NF-YB (HAP3) and NF-YC (HAP5) respectively. DrAp1 plays a key role in plant transition to flowering and ultimately in seed production (Laloum et al., 2013, Zotova et al., 2020). A portion of Dr1, the human TBP-associated protein, shows 71% amino acid sequence similarity to CBF-A (NF-YB, HAP3) (Sinha et al., 1996). Parts of the HAP3 and HAP5 proteins are similar to the archaebacterial histone-like protein HMf-2. HMf-2 forms a nucleosome-like DNA-protein complex, and the amino acid sequence of HMf-2 is similar to that of various histones. Hence, this motif of sequence similarity among HMf-2, (HAP3) CBF-A, and (HAP5) CBF-C is a histone-like motif (Sinha et al., 1996). Importantly, the C-terminal portion of this motif is present in Dr1, a human phosphoprotein associated with the TATA-binding protein TBP. Dr1 itself does not bind to DNA, but after it associates with TBP (TATA Binding Protein), it represses both basal and activated transcription of class II genes (Sinha et al., 1996).

To be classified as a CCAAT-DR1 TF the PFAM00808 motif (Histone-like transcription factor (CBF/NF-Y) and archaeal histone) should be present but not the PFAM02405 (CCAAT-binding transcription factor (CBF-B/NF-YA) subunit B), NF-YB, or NFYC motifs.

Last updated June 2023 by John Gray

References:

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