title: Transcriptomic assessment of resistance to effects of an aryl hydrocarbon receptor (AHR) agonist in embryos of Atlantic killifish (Fundulus heteroclitus) from a marine Superfund site.
abstract: BACKGROUND
  Populations of Atlantic killifish (Fundulus heteroclitus) have evolved resistance to the embryotoxic effects of polychlorinated biphenyls (PCBs) and other halogenated and nonhalogenated aromatic hydrocarbons that act through an aryl hydrocarbon receptor (AHR)-dependent signaling pathway. The resistance is accompanied by reduced sensitivity to induction of cytochrome P450 1A (CYP1A), a widely used biomarker of aromatic hydrocarbon exposure and effect, but whether the reduced sensitivity is specific to CYP1A or reflects a genome-wide reduction in responsiveness to all AHR-mediated changes in gene expression is unknown. We compared gene expression profiles and the response to 3,3',4,4',5-pentachlorobiphenyl (PCB-126) exposure in embryos (5 and 10 dpf) and larvae (15 dpf) from F. heteroclitus populations inhabiting the New Bedford Harbor, Massachusetts (NBH) Superfund site (PCB-resistant) and a reference site, Scorton Creek, Massachusetts (SC; PCB-sensitive).
  
  
  RESULTS
  Analysis using a 7,000-gene cDNA array revealed striking differences in responsiveness to PCB-126 between the populations; the differences occur at all three stages examined. There was a sizeable set of PCB-responsive genes in the sensitive SC population, a much smaller set of PCB-responsive genes in NBH fish, and few similarities in PCB-responsive genes between the two populations. Most of the array results were confirmed, and additional PCB-regulated genes identified, by RNA-Seq (deep pyrosequencing).
  
  
  CONCLUSIONS
  The results suggest that NBH fish possess a gene regulatory defect that is not specific to one target gene such as CYP1A but rather lies in a regulatory pathway that controls the transcriptional response of multiple genes to PCB exposure. The results are consistent with genome-wide disruption of AHR-dependent signaling in NBH fish.
authors: Rosenstiel School of Marine and Atmospheric Sciences, University of Miami, 4600 Rickenbacker Causeway, Miami, FL 33149 USA.
authors: Marjorie F
authors: MF
authors: Oleksiak
authors: Sibel I
authors: SI
authors: Karchner
authors: Matthew J
authors: MJ
authors: Jenny
authors: Diana G
authors: DG
authors: Franks
authors: David B Mark
authors: DB
authors: Welch
authors: Mark E
authors: ME
authors: Hahn
references: Aquat Toxicol. 2011 Jan 17;101(1):288-94
references: 21111492
references: Bioinformatics. 2004 Jun 12;20(9):1453-4
references: 14871861
references: Mol Ecol. 2009 Jul;18(13):2832-43
references: 19500250
references: Environ Toxicol Chem. 2003 Oct;22(10):2337-43
references: 14551997
references: Nat Genet. 2002 Oct;32(2):261-6
references: 12219088
references: Toxicol Sci. 2006 Aug;92(2):526-36
references: 16687390
references: Aquat Toxicol. 2008 Nov 21;90(3):161-71
references: 18929415
references: Mar Environ Res. 2004 Aug-Dec;58(2-5):119-24
references: 15178023
references: Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5425-30
references: 16567645
references: Crit Rev Eukaryot Gene Expr. 2008;18(3):207-50
references: 18540824
references: Curr Opin Genet Dev. 2002 Dec;12(6):683-7
references: 12433582
references: Environ Health Perspect. 2004 Dec;112(17):1658-64
references: 15579409
references: Science. 2011 Mar 11;331(6022):1322-5
references: 21330491
references: Br Foreign Med Chir Rev. 1860 Apr;25(50):367-404
references: 30164232
references: Aquat Toxicol. 2010 Jul 1;98(3):221-229
references: 20363516
references: Environ Toxicol Chem. 2002 Jul;21(7):1525-32
references: 12109755
references: Toxicol Sci. 2008 Sep;105(1):5-23
references: 18156145
references: J Biol Chem. 2002 Mar 1;277(9):6949-59
references: 11742002
references: Toxicol Sci. 2007 Jul;98(1):5-38
references: 17569696
references: Mol Ecol. 2010 Dec;19(23):5186-203
references: 20874759
references: Chem Res Toxicol. 2008 Sep;21(9):1651-71
references: 18707139
references: Pharmacogenetics. 2004 Feb;14(2):131-43
references: 15077014
references: Genet Res. 2001 Apr;77(2):123-8
references: 11355567
references: Mar Biotechnol (NY). 2001 Jun;3(Supplement 1):S203-11
references: 14961317
references: BMC Evol Biol. 2008 Oct 10;8:282
references: 18847479
references: J Cell Comp Physiol. 1959 Feb;53:1-11
references: 14445474
references: J Exp Zool. 1998 Sep-Oct 1;282(1-2):71-94
references: 9723168
references: Environ Toxicol Chem. 2009 Apr;28(4):759-71
references: 19391682
references: Annu Rev Pharmacol Toxicol. 1999;39:103-25
references: 10331078
references: Mol Pharmacol. 2006 Jan;69(1):140-53
references: 16214954
references: BMC Genet. 2010 Apr 30;11:32
references: 20433726
references: J Comput Biol. 2001;8(6):625-37
references: 11747616
references: Toxicol Sci. 2001 Mar;60(1):77-91
references: 11222875
references: Toxicol Sci. 2007 Nov;100(1):180-93
references: 17686920
references: Nature. 2005 Sep 15;437(7057):376-80
references: 16056220
references: Arch Toxicol. 2008 Nov;82(11):809-30
references: 18465118
references: Biostatistics. 2001 Jun;2(2):183-201
references: 12933549
references: Nat Genet. 2001 Dec;29(4):389-95
references: 11726925
references: Toxicol Sci. 2002 Jul;68(1):69-81
references: 12075112
references: PLoS One. 2009;4(2):e4486
references: 19221589
references: Aquat Toxicol. 2008 May 30;87(4):289-95
references: 18378331
references: Toxicol Appl Pharmacol. 1997 Jan;142(1):56-68
references: 9007034
references: Nat Genet. 2005 Jan;37(1):67-72
references: 15568023
references: Mol Pharmacol. 2004 Sep;66(3):512-21
references: 15322242
references: Aquat Toxicol. 2010 Aug 15;99(2):232-40
references: 20605646
references: Genet Res. 2006 Dec;88(3):153-63
references: 17371610
references: Comp Biochem Physiol Part D Genomics Proteomics. 2007 Dec;2(4):257-86
references: 18071578
references: J Biol Chem. 1999 Nov 19;274(47):33814-24
references: 10559277
references: Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9440-5
references: 12883005
references: Mol Pharmacol. 1994 Nov;46(5):915-21
references: 7969080
references: BMC Genomics. 2010 Apr 26;11:263
references: 20420666
references: Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13743-8
references: 9391097
references: Environ Toxicol Chem. 2002 Sep;21(9):1897-902
references: 12206429
references: Comp Biochem Physiol B Biochem Mol Biol. 2001 Mar;128(3):597-611
references: 11250554
references: BMC Genomics. 2007 Apr 25;8:108
references: 17459166
references: Toxicol Sci. 2000 Oct;57(2):229-39
references: 11006353
references: Mutat Res. 2004 Aug 18;552(1-2):73-100
references: 15288543
references: Toxicol Appl Pharmacol. 2011 Mar 1;251(2):119-29
references: 21215274
references: BMC Genomics. 2011 Feb 28;12:132
references: 21356103