The histone like NF-Y is a bifunctional transcription factor

Dipartimento di Scienze Biomolecolari e Biotecnologie, Università di Milano. Via Celoria 26 20133 Milano, Italy

^* To whom correspondence should be addressed. Email: mantor{at}unimi.it.

	Abstract

NF-Y is a trimeric transcription factor containing H2A/H2B-like subunits, which specifically binds to the CCAAT box, a common eukaryotic promoter element. To gain insights into NF-Y dependent transcriptional regulation, we assessed its relationships with positive histone marks by ChIP on chip and correlative profiling studies. Unbiased identification of binding sites shows that the majority of genes is bound by NF-Y, in the promoter and/or within the coding region. Parallel analysis of H3K9-14ac and H3K4me3 sites indicates that NF-Y loci can be divided in two distinct clusters: (i) a large cohort contains H3K9-14ac and H3K4me3 marks and correlates with expression. (ii) A sizeable group is devoid of these marks and is found on transcriptionally silent genes. Within this class, we find that NF-Y binding is associated to negative histone marks, such as H4K20me3 and H3K27me3. NF-Y removal by a Dominant Negative NF-YA leads to decrease in transcription of expressed genes associated with H3K4me3 and H3K9-14ac, while increasing the levels of many inactive genes. These data indicate that NF-Y is embedded in positive, as well as in negative methyl histone marks, serving a dual function in transcriptional regulation, as an activator or as a repressor.