AhR enriched regions without the DRE core were also verified, further demonstrating that the AhR can interact with DNA independent of a DRE core, but does not eliminate the possibility of AhR interaction through DNA looping or protein tethering. Interestingly, the fold enrichment values for regions with out the DRE core were consistently lower than those with a DRE core, suggesting read the full info here AhR interactions are stronger in regions containing a DRE. DRE Analysis of AhR Enriched Regions TCDD elicited changes in gene expression are mediated through AhR signaling via binding to the substitution intolerant DRE core sequence. Overlay ing TCDD induced AhR enrichment with DRE core loca tions throughout the mouse genome identified 57. 8% and 48. 5% of the enriched regions did not contain a DRE core regions at 2 and 24 hrs, respectively.

Other Inhibitors,Modulators,Libraries promoter specific ChIP chip stu dies have also reported DRE cores in 50% of the AhR Inhibitors,Modulators,Libraries enriched regions. The remaining enriched regions possessed at least one and as many as 16 DRE cores. AhR enriched regions with or without a DRE core exhibited similar widths Inhibitors,Modulators,Libraries and levels of enrichment. Matrix similarity scores have been calculated for each 19 bp DRE sequence within the mouse genome using a position weight matrix constructed from bona fide functional DREs. Of the 6,595 significant AhR enriched regions containing a DRE core, 90. 7% were within 500 bp of a DRE core with half of these positions located within 135 bp of a DRE core. However, only 8. 3% and 17. 8% of the AhR enriched regions at 2 and 24 hrs, respectively, possessed a putative functional DRE sequence sug gesting the AhR may bind other degenerate sequence elements.

AhR binding to an alternate Inhibitors,Modulators,Libraries response element has also been reported. Of the 8,353 and 472 enriched regions at 2 and 24 hrs, respectively, that did not contain a DRE core, 482 and 237, respectively, contained the alternate DRE sequence. The higher incidence of AhR enriched regions at 24 hrs containing the alternate response element may represent tertiary AhR binding sites resulting from conformational changes and crowd ing of the promoter with the general transcription machinery. Transcription Factor Binding Site Over Representation Analysis Significantly AhR enriched regions were computationally analyzed for over represented response elements for known TF binding site families using RegionMiner.

DREs as well other sites for early growth response, E2F, nuclear respiratory factor 1, nuclear receptor Inhibitors,Modulators,Libraries subfamily 2 factors and peroxisome proliferator activated receptor were over represented within AhR enriched regions. Many of these TF sites were enriched proximally to a DRE core suggesting possible interactions. Stu dies have previously reported interactions between AhR and many of these TFs. For example, AhR com plexes selleck inhibitor with EGR 1 following treatment of human HUVEC cells with high glucose concentrations.