The activity of the CCAAT-box binding factor NF-Y is modulated through theregulated expression of its a subunit during monocyte to macrophage differentiation: Regulation of tissue-specific genes through a ubiquitous transcription factor

In this study, we analyzed the regulation of NF-Y expression during human m onocyte to macrophage maturation. NF-Y is a ubiquitous and evolutionarily c onserved transcription factor that binds specifically to the CCAAT motif pr esent in the 5' promoter region of a wide variety of genes. We show here th at in circulating monocytes, NF-Y binding activity is not detected on the C CAAT motif present in the promoters of genes such as major histocompatibili ty complex (MHC) class II, gp91-phox, mig, and fibronectin, whereas during macrophage differentiation, a progressive increase in NF-Y binding activity is observed on these promoters. Analysis of NF-Y subunit expression indica tes that the absence of NF-Y activity in circulating monocytes is caused by a lack of the A subunit. Furthermore, addition of the recombinant NF-YA su bunit restores NF-Y binding. We show that the lack of NF-YA protein is due to posttranscriptional regulation and not to a specific proteolytic activit y. In fact, NF-YA mRNA is present at the same level at all days of monocyte cultivation, whereas the protein is absent in freshly isolated monocytes b ut is progressively synthesized during the maturation process. We thus conc lude that the NF-YA subunit plays a relevant role in activating transcripti on of genes highly expressed in mature monocytes. In line with this conclus ion, we show that the cut/CDP protein, a transcriptional repressor that inh ibits gpc91-phox gene expression by preventing NF-Y binding to the CAAT box , is absent in monocytes. (C) 1999 by The American Society of Hematology.