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• W3175702014 abstract "ABSTRACT The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor known for mediating the toxicity of 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) and related compounds. Although the canonical mechanism of AhR activation involves heterodimerization with the aryl hydrocarbon receptor nuclear translocator, other transcriptional regulators that interact with AhR have been identified. Enrichment analysis of motifs in AhR-bound genomic regions implicated co-operation with COUP transcription factor (COUP-TF) and hepatocyte nuclear factor 4 (HNF4). The present study investigated AhR, HNF4α and COUP-TFII genomic binding and effects on gene expression associated with liver-specific function and cell differentiation in response to TCDD. Hepatic ChIPseq data from male C57BL/6 mice at 2 hrs after oral gavage with 30 µg/kg TCDD were integrated with bulk RNA-sequencing (RNAseq) time-course (2 - 72 hrs) and dose-response (0.01 - 30 µg/kg) datasets to assess putative AhR, HNF4α and COUP-TFII interactions associated with differential gene expression. TCDD treatment resulted in the genomic enrichment of 23,701, 11,688, and 9,547 binding regions for AhR, COUP-TFII and HNF4α, respectively, throughout the genome. Functional enrichment analysis of differentially expressed genes (DEGs) identified differential binding enrichment for AhR, COUP-TFII, and HNF4a to regions within liver-specific genes suggesting intersections associated with the loss of liver-specific functions and hepatocyte differentiation. Analysis found that the repression of liver-specific, HNF4α target and hepatocyte differentiation genes, involved increased AhR and HNF4α binding with decreased COUP-TFII binding. Collectively, these results suggested TCDD-elicited loss of liver-specific functions and markers of hepatocyte differentiation involved interactions between AhR, COUP-TFII and HNF4α." @default.
• W3175702014 created "2021-07-05" @default.
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• W3175702014 date "2021-06-18" @default.
• W3175702014 modified "2023-10-15" @default.
• W3175702014 title "Genome-wide ChIPseq analysis of AhR, COUP-TF, and HNF4 enrichment in TCDD-treated mouse liver" @default.
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• W3175702014 doi "https://doi.org/10.1101/2021.06.18.448955" @default.
• W3175702014 hasPublicationYear "2021" @default.
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