Biochemistry of the Nuclear Factor Y

Before I get started, I would like to address the serious problem that I have with the geniuses of the world. Occasionally while reading the literature in my field, I begin to feel a strong wave of hopelessness wash over me. However, I was told by an elder at some point in my academic career that, "If you've made it this far, you're smart enough." Whenever I feel overwhelmed, I sit back, reflect, and run this quote through my mind. Back to the geniuses. An Italian molecular biologist named Roberto Mantovani is to thank for pioneering NF-Y research starting in the early 1990's and continuing through 2011 with his latest publication in PLoS.
In mammalian and plant systems, there are three NF-Y families, or subunits: NF-YA, NF-YB, and NF-YC. Mammalian biochemistry has revealed that the three subunits must form a trimer in order to properly bind DNA at the pentameric sequence CCAAT,  referred to as the CAT-box. Mammalian work has also shown that NF-Y posses compartment specificity. The working model is that NF-YB proteins and NF-YC proteins are localized primarily to the cytoplasm, until the B and C subunits dimerize. NF-YB "piggy-backs" on the NF-YC subunit, eventually penetrating the nuclear envelope. Once the B/C dimer has accessed the nucleus, the NF-YA/B/C trimer can bind sequence specific nucleotides in the promoters of genes. It is understood that the NF-Y trimer mimics an inverted triangle, with the A subunit occupying the apex. This apex, or A subunit is the only protein to physically contact the pentameric CAT-box. It is assumed that the B and C subunits grasp nucleotides flanking the CAT-box. This is important for a number of reasons. Nucleotides outside of the consensus sequence of ggCCAATct are not conserved, thus must be variable. This could explain NF-YB/C's loss of homology outside of the "conserved domain", which contains NF-YA/B/C binding domains and a DNA binding domain. Alternatively,  NF-YA subunits possess a conserved domain with almost twice the level of conservation as the B and C subunits.