Dioxin increases the interaction between aryl hydrocarbon receptor and estrogen receptor alpha at human promoters
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Dioxin increases the interaction between aryl hydrocarbon receptor and estrogen receptor alpha at human promoters. / Ahmed, Shaaima; Valen, Eivind; Sandelin, Albin Gustav; Matthews, Jason.
In: Toxicological Sciences, Vol. 111, No. 2, 2009, p. 254-266.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Dioxin increases the interaction between aryl hydrocarbon receptor and estrogen receptor alpha at human promoters
AU - Ahmed, Shaaima
AU - Valen, Eivind
AU - Sandelin, Albin Gustav
AU - Matthews, Jason
N1 - Key Words: aryl hydrocarbon receptor; estrogen receptor-; ChIP-chip; receptor crosstalk; dioxin.
PY - 2009
Y1 - 2009
N2 - Recent studies have shown that activated aryl hydrocarbon receptor (AHR) induced the recruitment of estrogen receptor- (ER) to AHR-regulated genes and that AHR is recruited to ER-regulated genes. However, these findings were limited to a small number of well-characterized AHR- or ER-responsive genes with little knowledge of what was occurring at other genomic regions. In this study, we showed using chromatin immunoprecipitation followed by hybridization to promoter focused microarrays (ChIP-chip) that 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment significantly increased the overlap of genomic regions bound by both AHR and ER. Conventional and sequential ChIPs confirmed the recruitment of AHR and ER to many of the identified regions. Transcription factor binding site analysis revealed an overrepresentation of aryl hydrocarbon receptor response elements in regions bound by both AHR and ER, suggesting that AHR was the important factor determining the recruitment of ER to these regions. RNA interference-mediated knockdown of AHR confirmed its requirement for the recruitment of ER to some, but not all, of the shared regions. Our findings demonstrate not only that dioxin induces the recruitment of ER to AHR target genes but also that AHR is recruited to estrogen-responsive regions in a gene-specific manner, suggesting that AHR utilizes both of these mechanisms to modulate estrogen-dependent signaling.
AB - Recent studies have shown that activated aryl hydrocarbon receptor (AHR) induced the recruitment of estrogen receptor- (ER) to AHR-regulated genes and that AHR is recruited to ER-regulated genes. However, these findings were limited to a small number of well-characterized AHR- or ER-responsive genes with little knowledge of what was occurring at other genomic regions. In this study, we showed using chromatin immunoprecipitation followed by hybridization to promoter focused microarrays (ChIP-chip) that 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment significantly increased the overlap of genomic regions bound by both AHR and ER. Conventional and sequential ChIPs confirmed the recruitment of AHR and ER to many of the identified regions. Transcription factor binding site analysis revealed an overrepresentation of aryl hydrocarbon receptor response elements in regions bound by both AHR and ER, suggesting that AHR was the important factor determining the recruitment of ER to these regions. RNA interference-mediated knockdown of AHR confirmed its requirement for the recruitment of ER to some, but not all, of the shared regions. Our findings demonstrate not only that dioxin induces the recruitment of ER to AHR target genes but also that AHR is recruited to estrogen-responsive regions in a gene-specific manner, suggesting that AHR utilizes both of these mechanisms to modulate estrogen-dependent signaling.
U2 - 10.1093/toxsci/kfp144
DO - 10.1093/toxsci/kfp144
M3 - Journal article
C2 - 19574409
VL - 111
SP - 254
EP - 266
JO - Toxicological Sciences
JF - Toxicological Sciences
SN - 1096-6080
IS - 2
ER -
ID: 13949409