Sequence features of retrotransposons allow for epigenetic variability

Transposable elements (TEs) are mobile genetic elements that make up a large fraction of mammalian genomes. While select TEs have been co-opted in host genomes to have function, the majority of these elements are epigenetically silenced by DNA methylation in somatic cells. However, some TEs in mice,...

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Autores principales:	Kevin R Costello, Amy Leung, Candi Trac, Michael Lee, Mudaser Basam, J Andrew Pospisilik, Dustin E Schones
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	variable methylation transposons IAPs Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/55ac6a019e3446ad92dcb3e7b15bda15
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spelling	oai:doaj.org-article:55ac6a019e3446ad92dcb3e7b15bda152021-11-05T16:15:27ZSequence features of retrotransposons allow for epigenetic variability10.7554/eLife.711042050-084Xe71104https://doaj.org/article/55ac6a019e3446ad92dcb3e7b15bda152021-10-01T00:00:00Zhttps://elifesciences.org/articles/71104https://doaj.org/toc/2050-084XTransposable elements (TEs) are mobile genetic elements that make up a large fraction of mammalian genomes. While select TEs have been co-opted in host genomes to have function, the majority of these elements are epigenetically silenced by DNA methylation in somatic cells. However, some TEs in mice, including the Intracisternal A-particle (IAP) subfamily of retrotransposons, have been shown to display interindividual variation in DNA methylation. Recent work has revealed that IAP sequence differences and strain-specific KRAB zinc finger proteins (KZFPs) may influence the methylation state of these IAPs. However, the mechanisms underlying the establishment and maintenance of interindividual variability in DNA methylation still remain unclear. Here, we report that sequence content and genomic context influence the likelihood that IAPs become variably methylated. IAPs that differ from consensus IAP sequences have altered KZFP recruitment that can lead to decreased KAP1 recruitment when in proximity of constitutively expressed genes. These variably methylated loci have a high CpG density, similar to CpG islands, and can be bound by ZF-CxxC proteins, providing a potential mechanism to maintain this permissive chromatin environment and protect from DNA methylation. These observations indicate that variably methylated IAPs escape silencing through both attenuation of KZFP binding and recognition by ZF-CxxC proteins to maintain a hypomethylated state.Kevin R CostelloAmy LeungCandi TracMichael LeeMudaser BasamJ Andrew PospisilikDustin E SchoneseLife Sciences Publications Ltdarticlevariable methylationtransposonsIAPsMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	variable methylation transposons IAPs Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	variable methylation transposons IAPs Medicine R Science Q Biology (General) QH301-705.5 Kevin R Costello Amy Leung Candi Trac Michael Lee Mudaser Basam J Andrew Pospisilik Dustin E Schones Sequence features of retrotransposons allow for epigenetic variability
description	Transposable elements (TEs) are mobile genetic elements that make up a large fraction of mammalian genomes. While select TEs have been co-opted in host genomes to have function, the majority of these elements are epigenetically silenced by DNA methylation in somatic cells. However, some TEs in mice, including the Intracisternal A-particle (IAP) subfamily of retrotransposons, have been shown to display interindividual variation in DNA methylation. Recent work has revealed that IAP sequence differences and strain-specific KRAB zinc finger proteins (KZFPs) may influence the methylation state of these IAPs. However, the mechanisms underlying the establishment and maintenance of interindividual variability in DNA methylation still remain unclear. Here, we report that sequence content and genomic context influence the likelihood that IAPs become variably methylated. IAPs that differ from consensus IAP sequences have altered KZFP recruitment that can lead to decreased KAP1 recruitment when in proximity of constitutively expressed genes. These variably methylated loci have a high CpG density, similar to CpG islands, and can be bound by ZF-CxxC proteins, providing a potential mechanism to maintain this permissive chromatin environment and protect from DNA methylation. These observations indicate that variably methylated IAPs escape silencing through both attenuation of KZFP binding and recognition by ZF-CxxC proteins to maintain a hypomethylated state.
format	article
author	Kevin R Costello Amy Leung Candi Trac Michael Lee Mudaser Basam J Andrew Pospisilik Dustin E Schones
author_facet	Kevin R Costello Amy Leung Candi Trac Michael Lee Mudaser Basam J Andrew Pospisilik Dustin E Schones
author_sort	Kevin R Costello
title	Sequence features of retrotransposons allow for epigenetic variability
title_short	Sequence features of retrotransposons allow for epigenetic variability
title_full	Sequence features of retrotransposons allow for epigenetic variability
title_fullStr	Sequence features of retrotransposons allow for epigenetic variability
title_full_unstemmed	Sequence features of retrotransposons allow for epigenetic variability
title_sort	sequence features of retrotransposons allow for epigenetic variability
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/55ac6a019e3446ad92dcb3e7b15bda15
work_keys_str_mv	AT kevinrcostello sequencefeaturesofretrotransposonsallowforepigeneticvariability AT amyleung sequencefeaturesofretrotransposonsallowforepigeneticvariability AT canditrac sequencefeaturesofretrotransposonsallowforepigeneticvariability AT michaellee sequencefeaturesofretrotransposonsallowforepigeneticvariability AT mudaserbasam sequencefeaturesofretrotransposonsallowforepigeneticvariability AT jandrewpospisilik sequencefeaturesofretrotransposonsallowforepigeneticvariability AT dustineschones sequencefeaturesofretrotransposonsallowforepigeneticvariability
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Sequence features of retrotransposons allow for epigenetic variability

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