Genome-wide computational analysis of dioxin response element location and distribution in the human, mouse, and rat
Edward Dere1, Agnes L Forgacs, Timothy R Zacharewski
1Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.
Abstract:
The aryl hydrocarbon receptor (AhR) mediates responses elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin by binding to dioxin response elements (DRE) containing the core consensus sequence 5'-GCGTG-3'. The human, mouse, and rat genomes were computationally searched for all DRE cores. Each core was then extended by 7 bp upstream and downstream, and matrix similarity (MS) scores for the resulting 19 bp DRE sequences were calculated using a revised position weight matrix constructed from bona fide functional DREs. In total, 72318 human, 70720 mouse, and 88651 rat high-scoring (MS ≥ 0.8437) putative DREs were identified. Gene-encoding intragenic DNA regions had ∼1.6 times more putative DREs than the noncoding intergenic DNA regions. Furthermore, the promoter region spanning ±1.5 kb of a TSS had the highest density of putative DREs within the genome. Chromosomal analysis found that the putative DRE densities of chromosomes X and Y were significantly lower than the mean chromosomal density. Interestingly, the 10 kb upstream promoter region on chromosome X of the genomes were significantly less dense than the chromosomal mean, while the same region in chromosome Y was the most dense. In addition to providing a detailed genomic map of all DRE cores in the human, mouse, and rat genomes, these data will further aid the elucidation of AhR-mediated signal transduction.
