Meta-Analysis of Transcriptome Data Detected New Potential Players in Response to Dioxin Exposure in Humans
Dioxins are one of the most potent anthropogenic poisons, causing systemic disorders in embryonic development and pathologies in adults. The mechanism of dioxin action requires an aryl hydrocarbon receptor (AhR), but the downstream mechanisms are not yet precisely clear. Here, we performed a meta-an...
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doaj-16cab78dfdac4805be68491391af2e742020-11-25T03:32:45ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-01217858785810.3390/ijms21217858Meta-Analysis of Transcriptome Data Detected New Potential Players in Response to Dioxin Exposure in HumansEvgeniya Oshchepkova0Yana Sizentsova1Daniil Wiebe2Victoria Mironova3Nikolay Kolchanov4Institute of Cytology and Genetics, 630090 Novosibirsk, RussiaInstitute of Cytology and Genetics, 630090 Novosibirsk, RussiaInstitute of Cytology and Genetics, 630090 Novosibirsk, RussiaInstitute of Cytology and Genetics, 630090 Novosibirsk, RussiaInstitute of Cytology and Genetics, 630090 Novosibirsk, RussiaDioxins are one of the most potent anthropogenic poisons, causing systemic disorders in embryonic development and pathologies in adults. The mechanism of dioxin action requires an aryl hydrocarbon receptor (AhR), but the downstream mechanisms are not yet precisely clear. Here, we performed a meta-analysis of all available transcriptome datasets taken from human cell cultures exposed to 2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxin (TCDD). Differentially expressed genes from different experiments overlapped partially, but there were a number of those genes that were systematically affected by TCDD. Some of them have been linked to toxic dioxin effects, but we also identified other attractive targets. Among the genes that were affected by TCDD, there are functionally related gene groups that suggest an interplay between retinoic acid, AhR, and Wnt signaling pathways. Next, we analyzed the upstream regions of differentially expressed genes and identified potential transcription factor (TF) binding sites overrepresented in the genes responding to TCDD. Intriguingly, the dioxin-responsive element (DRE), the binding site of AhR, was not overrepresented as much as other cis-elements were. Bioinformatics analysis of the AhR binding profile unveils potential cooperation of AhR with E2F2, CTCFL, and ZBT14 TFs in the dioxin response. We discuss the potential implication of these predictions for further dioxin studies.https://www.mdpi.com/1422-0067/21/21/7858dioxinaryl hydrocarbon receptormeta-analysistranscription factor binding sites |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Evgeniya Oshchepkova Yana Sizentsova Daniil Wiebe Victoria Mironova Nikolay Kolchanov |
spellingShingle |
Evgeniya Oshchepkova Yana Sizentsova Daniil Wiebe Victoria Mironova Nikolay Kolchanov Meta-Analysis of Transcriptome Data Detected New Potential Players in Response to Dioxin Exposure in Humans International Journal of Molecular Sciences dioxin aryl hydrocarbon receptor meta-analysis transcription factor binding sites |
author_facet |
Evgeniya Oshchepkova Yana Sizentsova Daniil Wiebe Victoria Mironova Nikolay Kolchanov |
author_sort |
Evgeniya Oshchepkova |
title |
Meta-Analysis of Transcriptome Data Detected New Potential Players in Response to Dioxin Exposure in Humans |
title_short |
Meta-Analysis of Transcriptome Data Detected New Potential Players in Response to Dioxin Exposure in Humans |
title_full |
Meta-Analysis of Transcriptome Data Detected New Potential Players in Response to Dioxin Exposure in Humans |
title_fullStr |
Meta-Analysis of Transcriptome Data Detected New Potential Players in Response to Dioxin Exposure in Humans |
title_full_unstemmed |
Meta-Analysis of Transcriptome Data Detected New Potential Players in Response to Dioxin Exposure in Humans |
title_sort |
meta-analysis of transcriptome data detected new potential players in response to dioxin exposure in humans |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-10-01 |
description |
Dioxins are one of the most potent anthropogenic poisons, causing systemic disorders in embryonic development and pathologies in adults. The mechanism of dioxin action requires an aryl hydrocarbon receptor (AhR), but the downstream mechanisms are not yet precisely clear. Here, we performed a meta-analysis of all available transcriptome datasets taken from human cell cultures exposed to 2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxin (TCDD). Differentially expressed genes from different experiments overlapped partially, but there were a number of those genes that were systematically affected by TCDD. Some of them have been linked to toxic dioxin effects, but we also identified other attractive targets. Among the genes that were affected by TCDD, there are functionally related gene groups that suggest an interplay between retinoic acid, AhR, and Wnt signaling pathways. Next, we analyzed the upstream regions of differentially expressed genes and identified potential transcription factor (TF) binding sites overrepresented in the genes responding to TCDD. Intriguingly, the dioxin-responsive element (DRE), the binding site of AhR, was not overrepresented as much as other cis-elements were. Bioinformatics analysis of the AhR binding profile unveils potential cooperation of AhR with E2F2, CTCFL, and ZBT14 TFs in the dioxin response. We discuss the potential implication of these predictions for further dioxin studies. |
topic |
dioxin aryl hydrocarbon receptor meta-analysis transcription factor binding sites |
url |
https://www.mdpi.com/1422-0067/21/21/7858 |
work_keys_str_mv |
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