Melanie Lindner1,2, Irene Verhagen3,4, Heidi M Viitaniemi5,6,7, Veronika N Laine3,8, Marcel E Visser3,9, Arild Husby5,10,11, Kees van Oers12. 1. Department of Animal Ecology, Netherlands Institute of Ecology (NIOO-KNAW), P.O. Box 50, Wageningen, 6700, AB, The Netherlands. m.lindner@nioo.knaw.nl. 2. Chronobiology Unit, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen, The Netherlands. m.lindner@nioo.knaw.nl. 3. Department of Animal Ecology, Netherlands Institute of Ecology (NIOO-KNAW), P.O. Box 50, Wageningen, 6700, AB, The Netherlands. 4. Wageningen University & Research, Wageningen, The Netherlands. 5. Organismal and Evolutionary Biology Research Programme, University of Helsinki, Helsinki, Finland. 6. Institute of Vertebrate Biology, Czech Academy of Sciences, Prague, Czech Republic. 7. Department of Biology, University of Turku, Turku, Finland. 8. Finnish Museum of Natural History, University of Helsinki, Helsinki, Finland. 9. Chronobiology Unit, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen, The Netherlands. 10. Evolutionary Biology, Department of Ecology and Genetics, Uppsala University, Uppsala, Sweden. 11. Department of Biology, NTNU, Centre for Biodiversity Dynamics, Trondheim, Norway. 12. Department of Animal Ecology, Netherlands Institute of Ecology (NIOO-KNAW), P.O. Box 50, Wageningen, 6700, AB, The Netherlands. k.vanoers@nioo.knaw.nl.
Abstract
BACKGROUND: DNA methylation is likely a key mechanism regulating changes in gene transcription in traits that show temporal fluctuations in response to environmental conditions. To understand the transcriptional role of DNA methylation we need simultaneous within-individual assessment of methylation changes and gene expression changes over time. Within-individual repeated sampling of tissues, which are essential for trait expression is, however, unfeasible (e.g. specific brain regions, liver and ovary for reproductive timing). Here, we explore to what extend between-individual changes in DNA methylation in a tissue accessible for repeated sampling (red blood cells (RBCs)) reflect such patterns in a tissue unavailable for repeated sampling (liver) and how these DNA methylation patterns are associated with gene expression in such inaccessible tissues (hypothalamus, ovary and liver). For this, 18 great tit (Parus major) females were sacrificed at three time points (n = 6 per time point) throughout the pre-laying and egg-laying period and their blood, hypothalamus, ovary and liver were sampled. RESULTS: We simultaneously assessed DNA methylation changes (via reduced representation bisulfite sequencing) and changes in gene expression (via RNA-seq and qPCR) over time. In general, we found a positive correlation between changes in CpG site methylation in RBCs and liver across timepoints. For CpG sites in close proximity to the transcription start site, an increase in RBC methylation over time was associated with a decrease in the expression of the associated gene in the ovary. In contrast, no such association with gene expression was found for CpG site methylation within the gene body or the 10 kb up- and downstream regions adjacent to the gene body. CONCLUSION: Temporal changes in DNA methylation are largely tissue-general, indicating that changes in RBC methylation can reflect changes in DNA methylation in other, often less accessible, tissues such as the liver in our case. However, associations between temporal changes in DNA methylation with changes in gene expression are mostly tissue- and genomic location-dependent. The observation that temporal changes in DNA methylation within RBCs can relate to changes in gene expression in less accessible tissues is important for a better understanding of how environmental conditions shape traits that temporally change in expression in wild populations.
BACKGROUND: DNA methylation is likely a key mechanism regulating changes in gene transcription in traits that show temporal fluctuations in response to environmental conditions. To understand the transcriptional role of DNA methylation we need simultaneous within-individual assessment of methylation changes and gene expression changes over time. Within-individual repeated sampling of tissues, which are essential for trait expression is, however, unfeasible (e.g. specific brain regions, liver and ovary for reproductive timing). Here, we explore to what extend between-individual changes in DNA methylation in a tissue accessible for repeated sampling (red blood cells (RBCs)) reflect such patterns in a tissue unavailable for repeated sampling (liver) and how these DNA methylation patterns are associated with gene expression in such inaccessible tissues (hypothalamus, ovary and liver). For this, 18 great tit (Parus major) females were sacrificed at three time points (n = 6 per time point) throughout the pre-laying and egg-laying period and their blood, hypothalamus, ovary and liver were sampled. RESULTS: We simultaneously assessed DNA methylation changes (via reduced representation bisulfite sequencing) and changes in gene expression (via RNA-seq and qPCR) over time. In general, we found a positive correlation between changes in CpG site methylation in RBCs and liver across timepoints. For CpG sites in close proximity to the transcription start site, an increase in RBC methylation over time was associated with a decrease in the expression of the associated gene in the ovary. In contrast, no such association with gene expression was found for CpG site methylation within the gene body or the 10 kb up- and downstream regions adjacent to the gene body. CONCLUSION: Temporal changes in DNA methylation are largely tissue-general, indicating that changes in RBC methylation can reflect changes in DNA methylation in other, often less accessible, tissues such as the liver in our case. However, associations between temporal changes in DNA methylation with changes in gene expression are mostly tissue- and genomic location-dependent. The observation that temporal changes in DNA methylation within RBCs can relate to changes in gene expression in less accessible tissues is important for a better understanding of how environmental conditions shape traits that temporally change in expression in wild populations.
Entities:
Keywords:
Accessible and inaccessible tissues; DNA methylation; Great tit; RNA expression; Tissue-specific and tissue-general temporal changes
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