Species Differences in the Effects of TCDD on a Transcriptional RegulatoryRegion within the Ig Heavy Chain Gene
| Main Author: | |
|---|---|
| Language: | English |
| Published: |
Wright State University / OhioLINK
2016
|
| Subjects: | |
| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=wright1464105119 |
| id |
ndltd-OhioLink-oai-etd.ohiolink.edu-wright1464105119 |
|---|---|
| record_format |
oai_dc |
| spelling |
ndltd-OhioLink-oai-etd.ohiolink.edu-wright14641051192021-08-03T06:36:52Z Species Differences in the Effects of TCDD on a Transcriptional RegulatoryRegion within the Ig Heavy Chain Gene Alfaheeda, Zahra J. Immunology Pharmaceuticals Toxicology immunology pharmaceuticals toxicology The immunoglobulin heavy chain gene (Igh) is regulated by numerous regulatory elements including the 3’Igh regulatory region (3’IghRR). Several transcription factors are involved in modulating the 3’IghRR including NF-¿B, AP-1, and the aryl hydrocarbon receptor (AhR). The AhR is a ligand-activated transcription factor that mediates the transcription of genes involved in the metabolism of environmental toxicants such as TCDD. TCDD binds AhR and regulates immunoglobulin (Ig) expression in B cells of animal models. This modulation appears to be directly mediated by binding of the AhR to dioxin response elements (DRE) within the 3’IghRR. Structural differences have been found between the human IGH and mouse Igh genes, including a duplication of the 3’IGHRR in humans and a polymorphic region in the human hs1.2 enhancer. This region is sensitive to TCCD-mediated modulation in mouse models whereas in in humans, several polymorphisms have been correlated with several autoimmune diseases. The objective of this study was to determine the transcriptional influence of human 3’IGHRR enhancer and sensitivity to TCDD. Using luciferase reporters controlled by the 3’IGHRR enhancers and cellular models including two well characterized B-cell lines: mouse CH12.LX and human CL-01. These cell lines can be induced to secrete Ig and can undergo class switch recombination. Our results suggest that, unlike mouse 3'IghRR, human 3'IGHRR is not sensitive to TCDD. Therefore, the role of this region remains to be determined. 2016-05-25 English text Wright State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=wright1464105119 http://rave.ohiolink.edu/etdc/view?acc_num=wright1464105119 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Immunology Pharmaceuticals Toxicology immunology pharmaceuticals toxicology |
| spellingShingle |
Immunology Pharmaceuticals Toxicology immunology pharmaceuticals toxicology Alfaheeda, Zahra J. Species Differences in the Effects of TCDD on a Transcriptional RegulatoryRegion within the Ig Heavy Chain Gene |
| author |
Alfaheeda, Zahra J. |
| author_facet |
Alfaheeda, Zahra J. |
| author_sort |
Alfaheeda, Zahra J. |
| title |
Species Differences in the Effects of TCDD on a Transcriptional RegulatoryRegion within the Ig Heavy Chain Gene |
| title_short |
Species Differences in the Effects of TCDD on a Transcriptional RegulatoryRegion within the Ig Heavy Chain Gene |
| title_full |
Species Differences in the Effects of TCDD on a Transcriptional RegulatoryRegion within the Ig Heavy Chain Gene |
| title_fullStr |
Species Differences in the Effects of TCDD on a Transcriptional RegulatoryRegion within the Ig Heavy Chain Gene |
| title_full_unstemmed |
Species Differences in the Effects of TCDD on a Transcriptional RegulatoryRegion within the Ig Heavy Chain Gene |
| title_sort |
species differences in the effects of tcdd on a transcriptional regulatoryregion within the ig heavy chain gene |
| publisher |
Wright State University / OhioLINK |
| publishDate |
2016 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=wright1464105119 |
| work_keys_str_mv |
AT alfaheedazahraj speciesdifferencesintheeffectsoftcddonatranscriptionalregulatoryregionwithintheigheavychaingene |
| _version_ |
1719440324220157952 |