Epigenetic landscape of 5-hydroxymethylcytosine and associations with gene expression in placenta
5-hydroxymethylcystosine (5hmC), is an intermediate product in the DNA demethylation pathway, but may act as a functional epigenetic modification. We have conducted the largest study of site-specific 5hmC in placenta to date using parallel bisulphite and oxidative bisulphite modification with array-...
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Taylor & Francis Group
2024-12-01
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| Series: | Epigenetics |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/15592294.2024.2326869 |
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| author | Michael Mortillo Elizabeth M. Kennedy Karen E. Hermetz Amber A. Burt Carmen J. Marsit |
| author_facet | Michael Mortillo Elizabeth M. Kennedy Karen E. Hermetz Amber A. Burt Carmen J. Marsit |
| author_sort | Michael Mortillo |
| collection | DOAJ |
| description | 5-hydroxymethylcystosine (5hmC), is an intermediate product in the DNA demethylation pathway, but may act as a functional epigenetic modification. We have conducted the largest study of site-specific 5hmC in placenta to date using parallel bisulphite and oxidative bisulphite modification with array-based assessment. Incorporating parallel RNA-sequencing data allowed us to assess associations between 5hmC and gene expression, using expression quantitative trait hydroxymethylation (eQTHM) analysis. We identified ~ 47,000 loci with consistently elevated (systematic) 5hmC proportions. Systematic 5hmC was significantly depleted (p < 0.0001) at CpG islands (CGI), and enriched (p < 0.0001) in ‘open sea’ regions (CpG >4 kb from CGI). 5hmC was most and least abundant at CpGs in enhancers and active transcription start sites (TSS), respectively (p < 0.05). We identified 499 significant (empirical-p <0.05) eQTHMs within 1 MB of the assayed gene. At most (75.4%) eQTHMs, the proportion of 5hmC was positively correlated with transcript abundance. eQTHMs were significantly enriched among enhancer CpGs and depleted among CpGs in active TSS (p < 0.05 for both). Finally, we identified 107 differentially hydroxymethylated regions (DHMRs, p < 0.05) across 100 genes. Our study provides insight into placental distribution of 5hmC, and sheds light on the functional capacity of this epigenetic modification in placenta. |
| format | Article |
| id | doaj-art-37b37fb99ca64922b632e1120751f889 |
| institution | Kabale University |
| issn | 1559-2294 1559-2308 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
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| series | Epigenetics |
| spelling | doaj-art-37b37fb99ca64922b632e1120751f8892024-12-09T07:21:35ZengTaylor & Francis GroupEpigenetics1559-22941559-23082024-12-0119110.1080/15592294.2024.2326869Epigenetic landscape of 5-hydroxymethylcytosine and associations with gene expression in placentaMichael Mortillo0Elizabeth M. Kennedy1Karen E. Hermetz2Amber A. Burt3Carmen J. Marsit4Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USAGangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USAGangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USAGangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USAGangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA5-hydroxymethylcystosine (5hmC), is an intermediate product in the DNA demethylation pathway, but may act as a functional epigenetic modification. We have conducted the largest study of site-specific 5hmC in placenta to date using parallel bisulphite and oxidative bisulphite modification with array-based assessment. Incorporating parallel RNA-sequencing data allowed us to assess associations between 5hmC and gene expression, using expression quantitative trait hydroxymethylation (eQTHM) analysis. We identified ~ 47,000 loci with consistently elevated (systematic) 5hmC proportions. Systematic 5hmC was significantly depleted (p < 0.0001) at CpG islands (CGI), and enriched (p < 0.0001) in ‘open sea’ regions (CpG >4 kb from CGI). 5hmC was most and least abundant at CpGs in enhancers and active transcription start sites (TSS), respectively (p < 0.05). We identified 499 significant (empirical-p <0.05) eQTHMs within 1 MB of the assayed gene. At most (75.4%) eQTHMs, the proportion of 5hmC was positively correlated with transcript abundance. eQTHMs were significantly enriched among enhancer CpGs and depleted among CpGs in active TSS (p < 0.05 for both). Finally, we identified 107 differentially hydroxymethylated regions (DHMRs, p < 0.05) across 100 genes. Our study provides insight into placental distribution of 5hmC, and sheds light on the functional capacity of this epigenetic modification in placenta.https://www.tandfonline.com/doi/10.1080/15592294.2024.2326869Hydroxymethylationgene expressioneQTHMplacenta |
| spellingShingle | Michael Mortillo Elizabeth M. Kennedy Karen E. Hermetz Amber A. Burt Carmen J. Marsit Epigenetic landscape of 5-hydroxymethylcytosine and associations with gene expression in placenta Epigenetics Hydroxymethylation gene expression eQTHM placenta |
| title | Epigenetic landscape of 5-hydroxymethylcytosine and associations with gene expression in placenta |
| title_full | Epigenetic landscape of 5-hydroxymethylcytosine and associations with gene expression in placenta |
| title_fullStr | Epigenetic landscape of 5-hydroxymethylcytosine and associations with gene expression in placenta |
| title_full_unstemmed | Epigenetic landscape of 5-hydroxymethylcytosine and associations with gene expression in placenta |
| title_short | Epigenetic landscape of 5-hydroxymethylcytosine and associations with gene expression in placenta |
| title_sort | epigenetic landscape of 5 hydroxymethylcytosine and associations with gene expression in placenta |
| topic | Hydroxymethylation gene expression eQTHM placenta |
| url | https://www.tandfonline.com/doi/10.1080/15592294.2024.2326869 |
| work_keys_str_mv | AT michaelmortillo epigeneticlandscapeof5hydroxymethylcytosineandassociationswithgeneexpressioninplacenta AT elizabethmkennedy epigeneticlandscapeof5hydroxymethylcytosineandassociationswithgeneexpressioninplacenta AT karenehermetz epigeneticlandscapeof5hydroxymethylcytosineandassociationswithgeneexpressioninplacenta AT amberaburt epigeneticlandscapeof5hydroxymethylcytosineandassociationswithgeneexpressioninplacenta AT carmenjmarsit epigeneticlandscapeof5hydroxymethylcytosineandassociationswithgeneexpressioninplacenta |