[
Genome Res,
1996]
If world oil prices dropped to zero next year, how would it change the world economy? Investments in oil field exploration would lose their value overnight, whereas shares in a factory making environmentally friendly combustion engines might go up. Everybody would feel the need to plan ahead, and many plans would change. In genetics and molecular biology, DNA sequences are the fuel of research, and their prices are falling dramatically. Within 5 years many complete genomes will be sequenced, and sequence data will be like tap water in Amsterdam-essential for life, but too cheap to measure. A project that was perfectly rational 2 years ago will be a total waste of time tomorrow, and projects that seemed impossible will become feasible. The aim of this review is to explore the consequences for biology of the wealth of DNA sequence data now becoming available. Several bacterial genomes have been sequenced already (Fleischmann et al. 1995; Fraser et al. 1995). The first animal to feel these changes will be the nematode Caenorhabditis elegans, and the worm" will be the focus of this review. The virtues of C. elegans as a model system in biology have recently been sung elsewhere (Hodgkin et al. 1995). In brief, it does everything that makes life interesting (eating, copulating, getting around, and relating to the environment) and manages to do so with only 959 cells, of which 302 form the brain. However, it is likely that much of what is said will apply equally to other species; thus, I hope that the review may also be of some interest outside of the C. elegans community.
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Crit Rev Biochem Mol Biol,
2012]
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; Hatamochi et al., 1988; Hooft van Huijsduijnen et al, 1987; Kim & Sheffery, 1990). A compelling set of bioinformatics studies clarified that the NF-Y preferred binding site is one of the most frequent promoter elements (Suzuki et al., 2001, 2004; Elkon et al., 2003; Marino-Ramirez et al., 2004; FitzGerald et al., 2004; Linhart et al., 2005; Zhu et al., 2005; Lee et al., 2007; Abnizova et al., 2007; Grskovic et al., 2007; Halperin et al., 2009; Hakkinen et al., 2011). The same consensus, as determined by mutagenesis and SELEX studies (Bi et al., 1997), was also retrieved in ChIP-on-chip analysis (Testa et al., 2005; Ceribelli et al., 2006; Ceribelli et al., 2008; Reed et al., 2008). Additional structural features of the CCAAT box - position, orientation, presence of multiple Transcriptional Start Sites - were previously reviewed (Dolfini et al., 2009) and will not be considered in detail here.