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Gene and transposable element methylation in great tit (Parus major) brain and blood

BACKGROUND: Studies on vertebrate DNA methylomes have revealed a regulatory role of tissue specific DNA methylation in relation to gene expression. However, it is not well known how tissue-specific methylation varies between different functional and structural components of genes and genomes. Using...

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Autores principales: Derks, Martijn F. L., Schachtschneider, Kyle M., Madsen, Ole, Schijlen, Elio, Verhoeven, Koen J. F., van Oers, Kees
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855439/
https://www.ncbi.nlm.nih.gov/pubmed/27146629
http://dx.doi.org/10.1186/s12864-016-2653-y
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author Derks, Martijn F. L.
Schachtschneider, Kyle M.
Madsen, Ole
Schijlen, Elio
Verhoeven, Koen J. F.
van Oers, Kees
author_facet Derks, Martijn F. L.
Schachtschneider, Kyle M.
Madsen, Ole
Schijlen, Elio
Verhoeven, Koen J. F.
van Oers, Kees
author_sort Derks, Martijn F. L.
collection PubMed
description BACKGROUND: Studies on vertebrate DNA methylomes have revealed a regulatory role of tissue specific DNA methylation in relation to gene expression. However, it is not well known how tissue-specific methylation varies between different functional and structural components of genes and genomes. Using whole-genome bisulfite sequencing data we here describe both CpG and non-CpG methylation profiles of whole blood and brain tissue in relation to gene features, CpG-islands (CGIs), transposable elements (TE), and their functional roles in an ecological model species, the great tit (Parus major). RESULTS: We show that hypomethylation at the transcription start site (TSS) is enriched in genes with functional classes that relate directly to processes specific to each tissue type. We find that 6877 (~21 %) of the CGIs are differentially methylated between blood and brain, of which 1186 and 2055 are annotated to promoter and intragenic regions, respectively. We observe that CGI methylation in promoter regions is more conserved between tissues compared to CGI methylation in intra and inter-genic regions. Differentially methylated CGIs in promoter and intragenic regions are overrepresented in genomic loci linked to development, suggesting a distinct role for CGI methylation in regulating expression during development. Additionally, we find significant non-CpG methylation in brain but not in blood with a strong preference for methylation at CpA dinucleotide sites. Finally, CpG hypermethylation of TEs is significantly stronger in brain compared to blood, but does not correlate with TE activity. Surprisingly, TEs showed significant hypomethylation in non-CpG contexts which was negatively correlated with TE expression. CONCLUSION: The discovery that TSS methylation levels are directly linked to functional classes related to each tissue provides new insights in the regulatory role of DNA-methylation patterns. The dominant sequence motifs for brain non-CpG methylation, similar to those found in mammals, suggests that a conserved non-CpG regulatory mechanism was already present in the amniote ancestor. The negative correlation between brain non-CpG methylation and TE activity (not found for CpG methylation) suggests that non-CpG is the dominant regulatory form of methylation in TE silencing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2653-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-48554392016-05-05 Gene and transposable element methylation in great tit (Parus major) brain and blood Derks, Martijn F. L. Schachtschneider, Kyle M. Madsen, Ole Schijlen, Elio Verhoeven, Koen J. F. van Oers, Kees BMC Genomics Research Article BACKGROUND: Studies on vertebrate DNA methylomes have revealed a regulatory role of tissue specific DNA methylation in relation to gene expression. However, it is not well known how tissue-specific methylation varies between different functional and structural components of genes and genomes. Using whole-genome bisulfite sequencing data we here describe both CpG and non-CpG methylation profiles of whole blood and brain tissue in relation to gene features, CpG-islands (CGIs), transposable elements (TE), and their functional roles in an ecological model species, the great tit (Parus major). RESULTS: We show that hypomethylation at the transcription start site (TSS) is enriched in genes with functional classes that relate directly to processes specific to each tissue type. We find that 6877 (~21 %) of the CGIs are differentially methylated between blood and brain, of which 1186 and 2055 are annotated to promoter and intragenic regions, respectively. We observe that CGI methylation in promoter regions is more conserved between tissues compared to CGI methylation in intra and inter-genic regions. Differentially methylated CGIs in promoter and intragenic regions are overrepresented in genomic loci linked to development, suggesting a distinct role for CGI methylation in regulating expression during development. Additionally, we find significant non-CpG methylation in brain but not in blood with a strong preference for methylation at CpA dinucleotide sites. Finally, CpG hypermethylation of TEs is significantly stronger in brain compared to blood, but does not correlate with TE activity. Surprisingly, TEs showed significant hypomethylation in non-CpG contexts which was negatively correlated with TE expression. CONCLUSION: The discovery that TSS methylation levels are directly linked to functional classes related to each tissue provides new insights in the regulatory role of DNA-methylation patterns. The dominant sequence motifs for brain non-CpG methylation, similar to those found in mammals, suggests that a conserved non-CpG regulatory mechanism was already present in the amniote ancestor. The negative correlation between brain non-CpG methylation and TE activity (not found for CpG methylation) suggests that non-CpG is the dominant regulatory form of methylation in TE silencing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2653-y) contains supplementary material, which is available to authorized users. BioMed Central 2016-05-04 /pmc/articles/PMC4855439/ /pubmed/27146629 http://dx.doi.org/10.1186/s12864-016-2653-y Text en © Derks et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Derks, Martijn F. L.
Schachtschneider, Kyle M.
Madsen, Ole
Schijlen, Elio
Verhoeven, Koen J. F.
van Oers, Kees
Gene and transposable element methylation in great tit (Parus major) brain and blood
title Gene and transposable element methylation in great tit (Parus major) brain and blood
title_full Gene and transposable element methylation in great tit (Parus major) brain and blood
title_fullStr Gene and transposable element methylation in great tit (Parus major) brain and blood
title_full_unstemmed Gene and transposable element methylation in great tit (Parus major) brain and blood
title_short Gene and transposable element methylation in great tit (Parus major) brain and blood
title_sort gene and transposable element methylation in great tit (parus major) brain and blood
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855439/
https://www.ncbi.nlm.nih.gov/pubmed/27146629
http://dx.doi.org/10.1186/s12864-016-2653-y
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