NF-Y and the transcriptional activation of CCAAT promoters

Abstract

The CCAAT box promoter element and NF-Y, the transcription factor (TF) that binds to it, were among the first cis-elements and trans-acting factors identified; their interplay is required for transcriptional activation of a sizeable number of eukaryotic genes. NF-Y consists of three evolutionarily conserved subunits: a dimer of NF-YB and NF-YC which closely resembles a histone, and the “innovative” NF-YA. In this review, we will provide an update on the functional and biological features that make NF-Y a fundamental link between chromatin and transcription.

The last 25 years have witnessed a spectacular increase in our knowledge of how genes are regulated: from the identification of cis-acting sequences in promoters and enhancers, and the biochemical characterization of the corresponding TFs, to the merging of chromatin studies with the investigation of enzymatic machines that regulate epigenetic states. Originally identified and studied in yeast and mammals, NF-Y – also termed CBF and CP1 – is composed of three subunits, NF-YA, NF-YB and NF-YC. The complex recognizes the CCAAT pentanucleotide and specific flanking nucleotides with high specificity (Dorn et al., 1997; ; ; ). A compelling set of bioinformatics studies clarified that the NF-Y preferred binding site is one of the most frequent promoter elements (; ; ; ; ; ; ; ; ; ; ). The same consensus, as determined by mutagenesis and SELEX studies (), was also retrieved in ChIP-on-chip analysis (; ; ; ). Additional structural features of the CCAAT box – position, orientation, presence of multiple Transcriptional Start Sites – were previously reviewed () and will not be considered in detail here.

Keywords::

• NF-Y
• transcription
• CCAAT box
• post-translational modification
• transcription factors and cofactors

Acknowledgements

We wish to thank D. Horner for reviewing the manuscript, the present and past members of the lab involved in NF-Y studies over the past decade, in particular C. Imbriano, M.C. Motta, G. Caretti, M. Frontini, A. di Silvio, C. Liberati, C. Vecchi, V. Salsi, A. Testa, G. Donati, M. Pitarque-Martì, B. Testoni, M. Ceribelli, L. Salvatoni, M.A. Viganò, D. Merico, C. Forni, G. Petrovich, A. Fossati. We also thank the many valuable collaborators over the years: P. Lievens, A. Ronchi, S. Ottolenghi, W. Reith, A. Farsetti, J. Golay, M. Introna, G. Marziali, D.Y. Shin, B. Trink, T.H. Huang, C. Kanduri, M. Ingelman-Sundberg, L. Tora, I. Davidson, C. Tonelli, C. Romier, D. Moras, M. d’Incalci, K. Scotto, K. Engeland, G. Piaggio, D. Hochhauser, J. Hartley, J. Ham. We apologize to the way too many colleagues whose valuable work could not be cited in this review.

Declaration of interest

The lab is supported by AIRC (5858), PRIN-MIUR (2008T9ZX9C), Regione Lombardia Proche (16782) and Nepente (14501) grants.

Editor: Michael M. Cox