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

M.F.L. Derks, K.M. Schachtschneider, O. Madsen, E.G.W.M. Schijlen, Koen J.F. Verhoeven, K. van Oers

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)

Abstract

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.
LanguageEnglish
Article number332
JournalBMC Genomics
Volume17
DOIs
Publication statusPublished - 2016

Fingerprint

DNA Transposable Elements
Methylation
CpG Islands
Brain
Genes
Transcription Initiation Site
Genetic Promoter Regions
Genome Components
Gene Components
DNA Methylation
Vertebrates
Mammals
Genome
Gene Expression

Cite this

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title = "Gene and transposable element methylation in great tit (Parus major) brain and blood",
abstract = "Background: Studies on vertebrate DNA methylomes have revealed a regulatory role of tissue specific DNAmethylation in relation to gene expression. However, it is not well known how tissue-specific methylation variesbetween different functional and structural components of genes and genomes. Using whole-genome bisulfitesequencing data we here describe both CpG and non-CpG methylation profiles of whole blood and brain tissue inrelation to gene features, CpG-islands (CGIs), transposable elements (TE), and their functional roles in an ecologicalmodel species, the great tit (Parus major).Results: We show that hypomethylation at the transcription start site (TSS) is enriched in genes with functionalclasses that relate directly to processes specific to each tissue type. We find that 6877 (~21 {\%}) of the CGIs aredifferentially methylated between blood and brain, of which 1186 and 2055 are annotated to promoter andintragenic regions, respectively. We observe that CGI methylation in promoter regions is more conserved betweentissues compared to CGI methylation in intra and inter-genic regions. Differentially methylated CGIs in promoterand intragenic regions are overrepresented in genomic loci linked to development, suggesting a distinct role forCGI methylation in regulating expression during development. Additionally, we find significant non-CpGmethylation 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 TEactivity. Surprisingly, TEs showed significant hypomethylation in non-CpG contexts which was negatively correlatedwith TE expression.Conclusion: The discovery that TSS methylation levels are directly linked to functional classes related to each tissueprovides new insights in the regulatory role of DNA-methylation patterns. The dominant sequence motifs for brainnon-CpG methylation, similar to those found in mammals, suggests that a conserved non-CpG regulatorymechanism was already present in the amniote ancestor. The negative correlation between brain non-CpGmethylation and TE activity (not found for CpG methylation) suggests that non-CpG is the dominant regulatoryform of methylation in TE silencing.",
author = "M.F.L. Derks and K.M. Schachtschneider and O. Madsen and E.G.W.M. Schijlen and Verhoeven, {Koen J.F.} and {van Oers}, K.",
year = "2016",
doi = "10.1186/s12864-016-2653-y",
language = "English",
volume = "17",
journal = "BMC Genomics",
issn = "1471-2164",
publisher = "Springer Verlag",

}

Gene and transposable element methylation in great tit (Parus major) brain and blood. / Derks, M.F.L.; Schachtschneider, K.M.; Madsen, O.; Schijlen, E.G.W.M.; Verhoeven, Koen J.F.; van Oers, K.

In: BMC Genomics, Vol. 17, 332, 2016.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Gene and transposable element methylation in great tit (Parus major) brain and blood

AU - Derks, M.F.L.

AU - Schachtschneider, K.M.

AU - Madsen, O.

AU - Schijlen, E.G.W.M.

AU - Verhoeven, Koen J.F.

AU - van Oers, K.

PY - 2016

Y1 - 2016

N2 - Background: Studies on vertebrate DNA methylomes have revealed a regulatory role of tissue specific DNAmethylation in relation to gene expression. However, it is not well known how tissue-specific methylation variesbetween different functional and structural components of genes and genomes. Using whole-genome bisulfitesequencing data we here describe both CpG and non-CpG methylation profiles of whole blood and brain tissue inrelation to gene features, CpG-islands (CGIs), transposable elements (TE), and their functional roles in an ecologicalmodel species, the great tit (Parus major).Results: We show that hypomethylation at the transcription start site (TSS) is enriched in genes with functionalclasses that relate directly to processes specific to each tissue type. We find that 6877 (~21 %) of the CGIs aredifferentially methylated between blood and brain, of which 1186 and 2055 are annotated to promoter andintragenic regions, respectively. We observe that CGI methylation in promoter regions is more conserved betweentissues compared to CGI methylation in intra and inter-genic regions. Differentially methylated CGIs in promoterand intragenic regions are overrepresented in genomic loci linked to development, suggesting a distinct role forCGI methylation in regulating expression during development. Additionally, we find significant non-CpGmethylation 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 TEactivity. Surprisingly, TEs showed significant hypomethylation in non-CpG contexts which was negatively correlatedwith TE expression.Conclusion: The discovery that TSS methylation levels are directly linked to functional classes related to each tissueprovides new insights in the regulatory role of DNA-methylation patterns. The dominant sequence motifs for brainnon-CpG methylation, similar to those found in mammals, suggests that a conserved non-CpG regulatorymechanism was already present in the amniote ancestor. The negative correlation between brain non-CpGmethylation and TE activity (not found for CpG methylation) suggests that non-CpG is the dominant regulatoryform of methylation in TE silencing.

AB - Background: Studies on vertebrate DNA methylomes have revealed a regulatory role of tissue specific DNAmethylation in relation to gene expression. However, it is not well known how tissue-specific methylation variesbetween different functional and structural components of genes and genomes. Using whole-genome bisulfitesequencing data we here describe both CpG and non-CpG methylation profiles of whole blood and brain tissue inrelation to gene features, CpG-islands (CGIs), transposable elements (TE), and their functional roles in an ecologicalmodel species, the great tit (Parus major).Results: We show that hypomethylation at the transcription start site (TSS) is enriched in genes with functionalclasses that relate directly to processes specific to each tissue type. We find that 6877 (~21 %) of the CGIs aredifferentially methylated between blood and brain, of which 1186 and 2055 are annotated to promoter andintragenic regions, respectively. We observe that CGI methylation in promoter regions is more conserved betweentissues compared to CGI methylation in intra and inter-genic regions. Differentially methylated CGIs in promoterand intragenic regions are overrepresented in genomic loci linked to development, suggesting a distinct role forCGI methylation in regulating expression during development. Additionally, we find significant non-CpGmethylation 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 TEactivity. Surprisingly, TEs showed significant hypomethylation in non-CpG contexts which was negatively correlatedwith TE expression.Conclusion: The discovery that TSS methylation levels are directly linked to functional classes related to each tissueprovides new insights in the regulatory role of DNA-methylation patterns. The dominant sequence motifs for brainnon-CpG methylation, similar to those found in mammals, suggests that a conserved non-CpG regulatorymechanism was already present in the amniote ancestor. The negative correlation between brain non-CpGmethylation and TE activity (not found for CpG methylation) suggests that non-CpG is the dominant regulatoryform of methylation in TE silencing.

U2 - 10.1186/s12864-016-2653-y

DO - 10.1186/s12864-016-2653-y

M3 - Article

VL - 17

JO - BMC Genomics

T2 - BMC Genomics

JF - BMC Genomics

SN - 1471-2164

M1 - 332

ER -