Cross-species transcriptomic analysis elucidates constitutive aryl hydrocarbon receptor activity

BMC Genomics

Paul C Boutros¹  Raimo Pohjanvirta³  Allan B Okey⁴  Christine P'ng²  Jere Lindén⁵  Sanna Lensu⁶  Ivy D Moffat⁴  John D Watson²  Stephenie D Prokopec²  Kathleen E Houlahan²  Trent T Simmons²  Lauren C Chong²  Ren X Sun² 

[1]MaRS Centre, 661 University Avenue, Suite 510, Toronto M5G 0A3 Ontario, Canada

[2]Informatics and Bio-computing Program, Ontario Institute for Cancer Research, Toronto, Canada

[3]Department of Food Hygiene and Environmental Health, University of Helsinki, Helsinki, Finland

[4]Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada

[5]Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland

[6]Department of Biology of Physical Activity, University of Jyväskylä, Jyväskylä, Finland

关键词: Core-gene battery;    TCDD-induced toxicity;    Constitutive gene expression;    AHR endogenous ligands;    Aryl hydrocarbon receptor;   

Others  :  1089972
DOI  :  10.1186/1471-2164-15-1053

 received in 2014-08-19, accepted in 2014-11-19,  发布年份 2014

【 摘 要 】

Background

Research on the aryl hydrocarbon receptor (AHR) has largely focused on variations in toxic outcomes resulting from its activation by halogenated aromatic hydrocarbons. But the AHR also plays key roles in regulating pathways critical for development, and after decades of research the mechanisms underlying physiological regulation by the AHR remain poorly characterized. Previous studies identified several core genes that respond to xenobiotic AHR ligands across a broad range of species and tissues. However, only limited inferences have been made regarding its role in regulating constitutive gene activity, i.e. in the absence of exogenous ligands. To address this, we profiled transcriptomic variations between AHR-active and AHR-less-active animals in the absence of an exogenous agonist across five tissues, three of which came from rats (hypothalamus, white adipose and liver) and two of which came from mice (kidney and liver). Because AHR status alone has been shown sufficient to alter transcriptomic responses, we reason that by contrasting profiles amongst AHR-variant animals, we may elucidate effects of the AHR on constitutive mRNA abundances.

Results

We found significantly more overlap in constitutive mRNA abundances amongst tissues within the same species than from tissues between species and identified 13 genes (Agt, Car3, Creg1, Ctsc, E2f6, Enpp1, Gatm, Gstm4, Kcnj8, Me1, Pdk1, Slc35a3, and Sqrdl) that are affected by AHR-status in four of five tissues. One gene, Creg1, was significantly up-regulated in all AHR-less-active animals. We also find greater overlap between tissues at the pathway level than at the gene level, suggesting coherency to the AHR signalling response within these processes. Analysis of regulatory motifs suggests that the AHR mostly mediates transcriptional regulation via direct binding to response elements.

Conclusions

These findings, though preliminary, present a platform for further evaluating the role of the AHR in regulation of constitutive mRNA levels and physiologic function.

【 授权许可】

   
2014 Sun et al.; licensee BioMed Central Ltd.

【 图 表 】

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