Weighted Gene Correlation Network Analysis (WGCNA) Reveals Novel Transcription Factors Associated With Bisphenol A Dose-Response
Despite Bisphenol-A (BPA) being subject to extensive study, a thorough understanding of molecular mechanism remains elusive. Here we show that using weighted gene correlation network analysis (WGCNA), which takes advantage of a graph theoretical approach to understanding correlations amongst genes a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2018.00508/full |
| _version_ | 1819067818277076992 |
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| author | Alexandra Maertens Vy Tran Andre Kleensang Thomas Hartung Thomas Hartung Thomas Hartung |
| author_facet | Alexandra Maertens Vy Tran Andre Kleensang Thomas Hartung Thomas Hartung Thomas Hartung |
| author_sort | Alexandra Maertens |
| collection | DOAJ |
| description | Despite Bisphenol-A (BPA) being subject to extensive study, a thorough understanding of molecular mechanism remains elusive. Here we show that using weighted gene correlation network analysis (WGCNA), which takes advantage of a graph theoretical approach to understanding correlations amongst genes and grouping genes into modules that typically have co-ordinated biological functions and regulatory mechanisms, that despite some commonality in altered genes, there is minimal overlap between BPA and estrogen in terms of network topology. We confirmed previous findings that ZNF217 and TFAP2C are involved in the estrogen pathway, and are implicated in BPA as well, although for BPA they appear to be active in the absence of canonical estrogen-receptor driven gene expression. Furthermore, our study suggested that PADI4 and RACK7/ZMYNDB8 may be involved in the overlap in gene expression between estradiol and BPA. Lastly, we demonstrated that even at low doses there are unique transcription factors that appear to be driving the biology of BPA, such as SREBF1. Overall, our data is consistent with other reports that BPA leads to subtle gene changes rather than profound aberrations of a conserved estrogen signaling (or other) pathways. |
| first_indexed | 2024-12-21T16:24:18Z |
| format | Article |
| id | doaj.art-0b4ea1f7e9de48058f8613676c50cfcf |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-21T16:24:18Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-0b4ea1f7e9de48058f8613676c50cfcf2022-12-21T18:57:29ZengFrontiers Media S.A.Frontiers in Genetics1664-80212018-11-01910.3389/fgene.2018.00508414481Weighted Gene Correlation Network Analysis (WGCNA) Reveals Novel Transcription Factors Associated With Bisphenol A Dose-ResponseAlexandra Maertens0Vy Tran1Andre Kleensang2Thomas Hartung3Thomas Hartung4Thomas Hartung5Center for Alternatives to Animal Testing, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United StatesCenter for Alternatives to Animal Testing, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United StatesCenter for Alternatives to Animal Testing, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United StatesCenter for Alternatives to Animal Testing, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United StatesCenter for Alternatives to Animal Testing - Europe, University of Konstanz, Konstanz, GermanyDoerenkamp-Zbinden Professor and Chair for Evidence-Based Toxicology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United StatesDespite Bisphenol-A (BPA) being subject to extensive study, a thorough understanding of molecular mechanism remains elusive. Here we show that using weighted gene correlation network analysis (WGCNA), which takes advantage of a graph theoretical approach to understanding correlations amongst genes and grouping genes into modules that typically have co-ordinated biological functions and regulatory mechanisms, that despite some commonality in altered genes, there is minimal overlap between BPA and estrogen in terms of network topology. We confirmed previous findings that ZNF217 and TFAP2C are involved in the estrogen pathway, and are implicated in BPA as well, although for BPA they appear to be active in the absence of canonical estrogen-receptor driven gene expression. Furthermore, our study suggested that PADI4 and RACK7/ZMYNDB8 may be involved in the overlap in gene expression between estradiol and BPA. Lastly, we demonstrated that even at low doses there are unique transcription factors that appear to be driving the biology of BPA, such as SREBF1. Overall, our data is consistent with other reports that BPA leads to subtle gene changes rather than profound aberrations of a conserved estrogen signaling (or other) pathways.https://www.frontiersin.org/article/10.3389/fgene.2018.00508/fullbisphenol AestrogenWGCNAZNF217TFAP2CZMYND8 |
| spellingShingle | Alexandra Maertens Vy Tran Andre Kleensang Thomas Hartung Thomas Hartung Thomas Hartung Weighted Gene Correlation Network Analysis (WGCNA) Reveals Novel Transcription Factors Associated With Bisphenol A Dose-Response Frontiers in Genetics bisphenol A estrogen WGCNA ZNF217 TFAP2C ZMYND8 |
| title | Weighted Gene Correlation Network Analysis (WGCNA) Reveals Novel Transcription Factors Associated With Bisphenol A Dose-Response |
| title_full | Weighted Gene Correlation Network Analysis (WGCNA) Reveals Novel Transcription Factors Associated With Bisphenol A Dose-Response |
| title_fullStr | Weighted Gene Correlation Network Analysis (WGCNA) Reveals Novel Transcription Factors Associated With Bisphenol A Dose-Response |
| title_full_unstemmed | Weighted Gene Correlation Network Analysis (WGCNA) Reveals Novel Transcription Factors Associated With Bisphenol A Dose-Response |
| title_short | Weighted Gene Correlation Network Analysis (WGCNA) Reveals Novel Transcription Factors Associated With Bisphenol A Dose-Response |
| title_sort | weighted gene correlation network analysis wgcna reveals novel transcription factors associated with bisphenol a dose response |
| topic | bisphenol A estrogen WGCNA ZNF217 TFAP2C ZMYND8 |
| url | https://www.frontiersin.org/article/10.3389/fgene.2018.00508/full |
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