Protein coding genes are transcribed by Polymerase II, under the control of short discrete DNA elements in promoters and enhancers, recognized with high efficiency and specificity by trans-acting factors and by general transcription proteins (Tjian and Maniatis, 1994). The former regulate specific genes or set of genes, usually in a tissue-, developmental-, cell-cycle or stimuli-dependent way; the latter are involved in the activation of all promoters, as a whole multi-subunit holoenzyme (Parvis and Young, 1998). A limited set of elements, such as the GC and CCAAT-boxes, are present in a very high number of promoters. The whole process is further complicated by the need to operate in the context of higher order chromatin structures (Workman and Kingston, 1998). This review focuses on the CCAAT sequence and on the NF-Y protein, also known as CBF, which binds to it.