The widespread distribution of intronic AREs and their particular association with HuR and HuR binding sites indicates that more than half of human genes can be regulated post-transcriptionally by AREs.
The structure of the binding sites indicates that lipid ligands are anchored within them with their hydrophobic tails oriented towards the core of the protein and their polar headgroups bound to charged sidechains at the mouth of the pockets.
Interestingly, the UCH L1 promoter revealed c-Myc and E2F binding sites indicating that UCH L1 might be playing a role in proliferation via these molecules.
Furthermore in HeLa cells, high resolution mapping of MBD2 binding sites indicated that MBD2 only associated the methylated region close to the TATA-box, whereas the unmethylated region, including the pS2 ERE, was not targeted by this repressor.
However, when considering the down-regulated genes compared to no-change genes, there was also a slight enrichment of STAT1 permuted binding sites, indicating that some of the observed effects may be non-specific (FIGURE S7C).
Of the 186 major Sty1 recruitment sites, 152 (∼82%) were found to overlap with the Atf1/Pcr1 binding sites (89 overlapped with the major Atf1/Pcr1 common binding sites and 63 with Atf1 and/or Pcr1 binding sites), indicating that Sty1 is primarily recruited at the Atf1/Pcr1 binding sites in the genome induced by H2O2 treatment.
Strikingly, examination of the promoters of the upregulated genes revealed an enrichment for E- and D-box binding sites, indicating that the role E- and D-box binding factors play in light induction of the per2 gene might also extend to many other light responsive genes.
Furthermore, through motif enrichment they found that genes in these clusters were enriched in AP1, JUN, CREB, ATF, EGR, and PPARA binding sites, indicating that components of our core response module may be regulated by the Fos/Jun AP1 complex, and the Egr1 and 2 transcription factors that are in the module as well.
Almost half of the conserved genes have validated ER binding sites indicating that they are direct ER targets.
Notably, a small nucleosome occupancy peak at the binding sites indicated that a tiny fraction of binding sites resided on nucleosomes.
