Genome-Wide Computational Analysis of Dioxin Response Element Location and Distribution in the Human, Mouse, and Rat Genomes

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.

芳香烃受体（aryl hydrocarbon receptor, AhR）可通过结合含有核心共有序列5′-GCGTG-3′的二噁英应答元件（dioxin response elements, DRE），介导2,3,7,8-四氯二苯并对二噁英（2,3,7,8-tetrachlorodibenzo-p-dioxin）诱导的生物学应答。本研究通过计算手段，在人、小鼠和大鼠的全基因组中检索所有DRE核心序列。随后对每个核心序列上下游各延伸7个碱基对，利用基于真实功能性DRE构建的修正位置权重矩阵（position weight matrix），计算所得19 bp长度DRE序列的矩阵相似度（matrix similarity, MS）得分。最终共鉴定得到72318个人类、70720个小鼠以及88651个大鼠的高评分（MS ≥ 0.8437）候选DRE。编码基因的基因内DNA区域的候选DRE数量约为非编码基因间DNA区域的1.6倍。此外，转录起始位点（transcription start site, TSS）上下游±1.5 kb范围内的启动子区域，是全基因组中候选DRE密度最高的区域。染色体分析结果显示，X染色体与Y染色体的候选DRE密度显著低于染色体平均密度。值得注意的是，各基因组X染色体上10 kb上游启动子区域的候选DRE密度显著低于染色体平均水平，而Y染色体上的相同区域则为密度最高的区域。本研究不仅完成了人、小鼠和大鼠全基因组中所有DRE核心序列的详细基因组图谱绘制，相关数据还将进一步助力解析AhR介导的信号转导过程。