CCAAT-box regulatory DNA element (CCAAT box)

The CCAAT-box regulatory DNA element, often identified by its reverse-complement sequence ATTGG, is a highly conserved cis-acting motif located in the proximal promoters of approximately 25-30% of eukaryotic genes (Mantovani, 1999). This site serves as the primary binding target for the heterotrimeric transcription factor Nuclear Factor Y (NF-Y), which acts as a pioneer factor to modulate chromatin accessibility and facilitate the recruitment of the basal transcription machinery (Petroni et al., 2017). These regulatory regions are critical for the expression of genes governing the cell cycle, DNA synthesis, and metabolic pathways, such as Cyclin B1 and Topoisomerase II alpha (Dolfini et al., 2012). In various malignancies, the over-activation or increased accessibility of ATTGG-containing regions drives oncogenic gene expression programs, contributing to tumor proliferation and survival (Gurtner et al., 2003). Therapeutic strategies targeting these DNA regions involve small molecules like Mithramycin A and its analogues, which bind to the DNA minor groove to sterically hinder NF-Y binding and suppress the transcription of its target oncogenes (Gurtner et al., 2003). However, the ubiquitous presence of the CCAAT motif across the genome poses significant challenges, including potential systemic toxicity and the inhibition of essential housekeeping genes in healthy tissues (Petroni et al., 2017).

Other names

ATTGG-containing regulatory regionNF-Y binding siteCCAAT elementNuclear Factor Y binding siteCBF binding site

DNA minor groove binding and competitive displacement of transcription factors