NF-Y is associated with the histone acetyltransferases GCN5 and P/CAF.
The ubiquitous transcription factor, NF-Y, plays a pivotal role in the cell cycle regulation of the mammalian cyclin A, cdc25C, and cdc2 genes, in the S-phase activation of the ribonucleotide reductase R2 gene, in addition to its critical role as a key proximal promoter factor in the transcriptional regulation of the albumin, collagen, lipoprotein lipase, major histocompatibility complex class II, and a variety of other eukaryotic and viral genes. In this report, the NF-Y complex has been shown to possess histone acetyltransferase activity through physical association with the related histone acetyltransferase enzymes, human GCN5 and P/CAF in vivo. The assembled NF-YA:B:C complex, and the NF-YB:YC, NF-YB:YC (DNA binding-subunit interaction domain), and NF-YC:YB (DNA binding-subunit interaction domain) heterodimers were sufficient to support stable interaction with human GCN5 in vitro, suggesting that these histone acetyltransferases interact with a unique surface in the ancient YB:YC histone-fold motif. Deletion of either N- or C-terminal regions in human GCN5 disrupted interaction with NF-Y in vitro. In addition, human GCN5 was observed to activate NF-Y in transient transfections in vivo using a natural alpha 2(I) collagen promoter. These results suggest that these associated histone acetyltransferases may serve to modulate NF-Y transactivation potential by aiding disruption of local chromatin structure thereby facilitating NF-Y access to its CCAAT box DNA binding sites.
Currie
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RA
Laboratory of Gene Regulation, Picower Institute for Medical Research, Manhasset, New York 11030, USA.
D000123:Acetyltransferases / Q000378:metabolism*; D022762:CCAAT-Enhancer-Binding Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006801:Humans; D010101:Oxygen Consumption / Q000235:genetics; D011485:Protein Binding; D017510:Protein Folding; D012441:Saccharomyces cerevisiae; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D022762:CCAAT-Enhancer-Binding Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C501179:KAT2A protein, human