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Trends Genet,
1999]
Communication with the environment and other animals through chemical cues is an essential process for the survival of many multicellular organisms. Specialized signal transduction pathways are employed in chemodetection and the transformation of information into the electrical signals that elicit behaviors. In organisms as diverse as mice and nematodes, similar molecules are involved in the odorant signaling pathways. Studying the mechanisms of signal transduction in these two systems using biochemical, molecular and genetic approaches has elucidated pathways for odor perception and the roles of specific proteins and second messenger molecules in the signaling cascades.
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Curr Opin Genet Dev,
1995]
Our understanding of olfaction has progressed rapidly in recent years as a result of the molecular genetic approaches being used to study this sensory system in a variety of model organisms. Considerable success has been achieved in identifying proteins of the mammalian signaling system that are analogous to those present in other sensory systems. More recently, genetic selection of mutations that cause defects in olfactory function in Drosophila melanogaster and Caenorhabditis elegans has led to the identification of additional proteins that play a role in the detection of odorants. The application of genetic, electrophysiological, and molecular analyses to olfactory function in mammals is also shedding light on the mechanisms that account for sensitivity and specificity in this system.
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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.