Figure 4: DNA-binding modes of NRs implicated in HNSCC. RAR can heterodimerize with PPARs, which can be activated by lipophilic ligands. Alternatively, RARs are able to heterodimerize with RXRs, which are activated by 9-cis RA. Such heterodimers can bind to specific half-site retinoic acid (RARE) or peroxisome proliferator response elements (PPREs) direct repeats in the DNA of target genes. Estradiol binding induces estrogen receptor homodimerization and binding to palindromic half-site estrogen response element (ERE) inverted repeats. N: Any nucleotide occurring within the specific response element.