Genomic properties of variably methylated retrotransposons in mouse
Abstract Background Transposable elements (TEs) are enriched in cytosine methylation, preventing their mobility within the genome. We previously identified a genome-wide repertoire of candidate intracisternal A particle (IAP) TEs in mice that exhibit inter-individual variability in this methylation...
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doaj-adf7dc0066924ceb83c4919b87a039672021-02-23T09:12:41ZengBMCMobile DNA1759-87532021-02-0112111610.1186/s13100-021-00235-1Genomic properties of variably methylated retrotransposons in mouseJessica L. Elmer0Amir D. Hay1Noah J. Kessler2Tessa M. Bertozzi3Eve A. C. Ainscough4Anne C. Ferguson-Smith5Department of Genetics, University of CambridgeDepartment of Genetics, University of CambridgeDepartment of Genetics, University of CambridgeDepartment of Genetics, University of CambridgeDepartment of Genetics, University of CambridgeDepartment of Genetics, University of CambridgeAbstract Background Transposable elements (TEs) are enriched in cytosine methylation, preventing their mobility within the genome. We previously identified a genome-wide repertoire of candidate intracisternal A particle (IAP) TEs in mice that exhibit inter-individual variability in this methylation (VM-IAPs) with implications for genome function. Results Here we validate these metastable epialleles and discover a novel class that exhibit tissue specificity (tsVM-IAPs) in addition to those with uniform methylation in all tissues (constitutive- or cVM-IAPs); both types have the potential to regulate genes in cis. Screening for variable methylation at other TEs shows that this phenomenon is largely limited to IAPs, which are amongst the youngest and most active endogenous retroviruses. We identify sequences enriched within cVM-IAPs, but determine that these are not sufficient to confer epigenetic variability. CTCF is enriched at VM-IAPs with binding inversely correlated with DNA methylation. We uncover dynamic physical interactions between cVM-IAPs with low methylation ranges and other genomic loci, suggesting that VM-IAPs have the potential for long-range regulation. Conclusion Our findings indicate that a recently evolved interplay between genetic sequence, CTCF binding, and DNA methylation at young TEs can result in inter-individual variability in transcriptional outcomes with implications for phenotypic variation.https://doi.org/10.1186/s13100-021-00235-1RetrotransposonEndogenous retrovirusIntracisternal A particleDNA methylationMetastable epialleleCTCF |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jessica L. Elmer Amir D. Hay Noah J. Kessler Tessa M. Bertozzi Eve A. C. Ainscough Anne C. Ferguson-Smith |
spellingShingle |
Jessica L. Elmer Amir D. Hay Noah J. Kessler Tessa M. Bertozzi Eve A. C. Ainscough Anne C. Ferguson-Smith Genomic properties of variably methylated retrotransposons in mouse Mobile DNA Retrotransposon Endogenous retrovirus Intracisternal A particle DNA methylation Metastable epiallele CTCF |
author_facet |
Jessica L. Elmer Amir D. Hay Noah J. Kessler Tessa M. Bertozzi Eve A. C. Ainscough Anne C. Ferguson-Smith |
author_sort |
Jessica L. Elmer |
title |
Genomic properties of variably methylated retrotransposons in mouse |
title_short |
Genomic properties of variably methylated retrotransposons in mouse |
title_full |
Genomic properties of variably methylated retrotransposons in mouse |
title_fullStr |
Genomic properties of variably methylated retrotransposons in mouse |
title_full_unstemmed |
Genomic properties of variably methylated retrotransposons in mouse |
title_sort |
genomic properties of variably methylated retrotransposons in mouse |
publisher |
BMC |
series |
Mobile DNA |
issn |
1759-8753 |
publishDate |
2021-02-01 |
description |
Abstract Background Transposable elements (TEs) are enriched in cytosine methylation, preventing their mobility within the genome. We previously identified a genome-wide repertoire of candidate intracisternal A particle (IAP) TEs in mice that exhibit inter-individual variability in this methylation (VM-IAPs) with implications for genome function. Results Here we validate these metastable epialleles and discover a novel class that exhibit tissue specificity (tsVM-IAPs) in addition to those with uniform methylation in all tissues (constitutive- or cVM-IAPs); both types have the potential to regulate genes in cis. Screening for variable methylation at other TEs shows that this phenomenon is largely limited to IAPs, which are amongst the youngest and most active endogenous retroviruses. We identify sequences enriched within cVM-IAPs, but determine that these are not sufficient to confer epigenetic variability. CTCF is enriched at VM-IAPs with binding inversely correlated with DNA methylation. We uncover dynamic physical interactions between cVM-IAPs with low methylation ranges and other genomic loci, suggesting that VM-IAPs have the potential for long-range regulation. Conclusion Our findings indicate that a recently evolved interplay between genetic sequence, CTCF binding, and DNA methylation at young TEs can result in inter-individual variability in transcriptional outcomes with implications for phenotypic variation. |
topic |
Retrotransposon Endogenous retrovirus Intracisternal A particle DNA methylation Metastable epiallele CTCF |
url |
https://doi.org/10.1186/s13100-021-00235-1 |
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