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TCDD

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Full-Text Articles in Pharmacology, Toxicology and Environmental Health

Ahr-Mediated Transcriptional Regulation Of The Human Immunoglobulin Hs1.2 Enhancer, Sydney White Jan 2022

Ahr-Mediated Transcriptional Regulation Of The Human Immunoglobulin Hs1.2 Enhancer, Sydney White

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The 3'IGHRR is thought to be responsible for the transcription of the immunoglobulin heavy chain (IGH) gene locus, which is essential for the production of antibodies. The human 3’IGHRR, which is duplicated in humans, contains the hs3, hs4, and hs1.2 enhancers. Additionally, the hs1.2 enhancer is polymorphic in humans and consists of a 53 bp invariant sequence that can be repeated one to four times. Previous experiments in a mouse and human B-cell line model have shown that the high affinity AhR ligand and environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can induce hs1.2 enhancer activity in an AhR-dependent manner. The AhR is …


The Aryl Hydrocarbon Receptor Regulates An Essential Transcriptional Element In The Immunoglobulin Heavy Chain Gene, Michael J. Wourms Jan 2013

The Aryl Hydrocarbon Receptor Regulates An Essential Transcriptional Element In The Immunoglobulin Heavy Chain Gene, Michael J. Wourms

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2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant that inhibits immunoglobulin (Ig) expression and Ig heavy (IgH) chain gene transcription. Transcription of the IgH gene involves several regulatory elements including the 3'lgh regulatory region (3'lghRR) which is composed of four enhancers (hs3A, hs1,2, hs4, and hs3B). Dioxin responsive elements (DRE) in the hs4 and hs1,2 enhancers of the 3lghRR that bind the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that regulates dioxin sensitive genes suggest that the 3'lghRR may be a transcriptional target of TCDD. The current study utilized an IgA secreting mouse …


Elucidating Transcription Factor Regulation By Tcdd Within The Hs1,2 Enhancer, Sharon D. Ochs Jan 2012

Elucidating Transcription Factor Regulation By Tcdd Within The Hs1,2 Enhancer, Sharon D. Ochs

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Immunoglobulin heavy chain (IgH) expression and Ig secretion is inhibited by the environmental contaminant 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD). Within the IgH gene, the 3' IgH regulatory region (3'IgH RR) has been identified as a transcriptional target of TCDD. The 3'IgH RR, which in part regulates transcription of the IgH gene, is composed of four enhancers in the mouse: hs3a; hs1,2; h3b; hs4 and three enhancers in the human: hs3a; hs1,2; hs4. In humans the hs1,2 enhancer has an invariant sequence (IS) containing a DRE, NF-κB, NF1 and AP-1 binding site. Also, the enhancer has an AP1.ETS and Oct …


2,3,7,8-Tetrachlordibenzo-P-Dioxin Mediated Immune Suppression Through Interactions At The 3'Immunoglobulin Heavy Chain Regulatory Region Enhancers, David Harold Ellis Jan 2010

2,3,7,8-Tetrachlordibenzo-P-Dioxin Mediated Immune Suppression Through Interactions At The 3'Immunoglobulin Heavy Chain Regulatory Region Enhancers, David Harold Ellis

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2,3,7,8-Tetrachlordibenzo-p-dioxin (TCDD) is a potent toxin which inhibits the antibody response of B cells. The 3'IgHRR which is involved in transcriptional regulation of the heavy-chain polypeptide of antibodies is inhibited by TCDD. The hs1,2 enhancer region, isolated from the 3'IgHRR, is also inhibited while the isolated hs4 is activated by TCDD. This project sought to determine if that dichotomy in effects results from interactions at enhancer-specific binding sites for AhR, thought to mediate transcriptional effects of TCDD, and NFκB, a transcription factor involved in B cell activation. Here, I report a difference in the effect of TCDD on transcriptional activity …


Tcdd-Induced Modulation Of The Hs1,2 Enhancer Within The 3'Immunoglobulin Heavy Chain Regulatory Region, Tharu M. Fernando Jan 2009

Tcdd-Induced Modulation Of The Hs1,2 Enhancer Within The 3'Immunoglobulin Heavy Chain Regulatory Region, Tharu M. Fernando

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2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent environmental toxin that inhibits immunoglobulin (Ig) gene expression in mice. Transcriptional regulation of the Ig heavy chain (IgH) involves the 3'IgH regulatory region (3'IgH RR). The murine 3'IgH RR consists of four enhancers (hs3A, hs1,2, hs3B, and hs4), which are homologous to the human 3'IgH RR enhancers (hs3, hs1,2, and hs4). In humans, a polymorphism of the hs1,2 enhancer, resulting in a varying number of tandem repeats of a 53 bp sequence, has been correlated with autoimmune diseases like IgA nephropathy and Celiac disease. The repeated sequence contains a kB and DRE binding site. Previous …