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CpG Methylation of a Silent Controlling Element in the Murine A(vy) Allele Is Incomplete and Unresponsive to Methyl Donor Supplementation

BACKGROUND: The viable yellow allele of agouti (A(vy)) is remarkable for its unstable and partially heritable epigenetic state, which produces wide variation in phenotypes of isogenic mice. In the A(vy) allele an inserted intracisternal A particle (IAP) acts as a controlling element which deregulate...

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Autores principales: Cropley, Jennifer E., Suter, Catherine M., Beckman, Kenneth B., Martin, David I. K.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816220/
https://www.ncbi.nlm.nih.gov/pubmed/20140227
http://dx.doi.org/10.1371/journal.pone.0009055
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author Cropley, Jennifer E.
Suter, Catherine M.
Beckman, Kenneth B.
Martin, David I. K.
author_facet Cropley, Jennifer E.
Suter, Catherine M.
Beckman, Kenneth B.
Martin, David I. K.
author_sort Cropley, Jennifer E.
collection PubMed
description BACKGROUND: The viable yellow allele of agouti (A(vy)) is remarkable for its unstable and partially heritable epigenetic state, which produces wide variation in phenotypes of isogenic mice. In the A(vy) allele an inserted intracisternal A particle (IAP) acts as a controlling element which deregulates expression of agouti by transcription from the LTR of the IAP; the phenotypic state has been linked to CpG methylation of the LTR. Phenotypic variation between A(vy) mice indicates that the epigenetic state of the IAP is unstable in the germline. PRINCIPAL FINDINGS: We have made a detailed examination of somatic methylation of the IAP using bisulphite allelic sequencing, and find that the promoter is incompletely methylated even when it is transcriptionally silent. In utero exposure to supplementary methyl donors, which alters the spectrum of A(vy) phenotypes, does not increase the density of CpG methylation in the silent LTR. CONCLUSIONS: Our findings suggest that, contrary to previous supposition, methyl donor supplementation acts through an indirect mechanism to silence A(vy). The incomplete cytosine methylation we observe at the somatically silent A(vy) allele may reflect its unstable germline state, and the influence of epigenetic modifications underlying CpG methylation.
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spelling pubmed-28162202010-02-07 CpG Methylation of a Silent Controlling Element in the Murine A(vy) Allele Is Incomplete and Unresponsive to Methyl Donor Supplementation Cropley, Jennifer E. Suter, Catherine M. Beckman, Kenneth B. Martin, David I. K. PLoS One Research Article BACKGROUND: The viable yellow allele of agouti (A(vy)) is remarkable for its unstable and partially heritable epigenetic state, which produces wide variation in phenotypes of isogenic mice. In the A(vy) allele an inserted intracisternal A particle (IAP) acts as a controlling element which deregulates expression of agouti by transcription from the LTR of the IAP; the phenotypic state has been linked to CpG methylation of the LTR. Phenotypic variation between A(vy) mice indicates that the epigenetic state of the IAP is unstable in the germline. PRINCIPAL FINDINGS: We have made a detailed examination of somatic methylation of the IAP using bisulphite allelic sequencing, and find that the promoter is incompletely methylated even when it is transcriptionally silent. In utero exposure to supplementary methyl donors, which alters the spectrum of A(vy) phenotypes, does not increase the density of CpG methylation in the silent LTR. CONCLUSIONS: Our findings suggest that, contrary to previous supposition, methyl donor supplementation acts through an indirect mechanism to silence A(vy). The incomplete cytosine methylation we observe at the somatically silent A(vy) allele may reflect its unstable germline state, and the influence of epigenetic modifications underlying CpG methylation. Public Library of Science 2010-02-04 /pmc/articles/PMC2816220/ /pubmed/20140227 http://dx.doi.org/10.1371/journal.pone.0009055 Text en Cropley et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Cropley, Jennifer E.
Suter, Catherine M.
Beckman, Kenneth B.
Martin, David I. K.
CpG Methylation of a Silent Controlling Element in the Murine A(vy) Allele Is Incomplete and Unresponsive to Methyl Donor Supplementation
title CpG Methylation of a Silent Controlling Element in the Murine A(vy) Allele Is Incomplete and Unresponsive to Methyl Donor Supplementation
title_full CpG Methylation of a Silent Controlling Element in the Murine A(vy) Allele Is Incomplete and Unresponsive to Methyl Donor Supplementation
title_fullStr CpG Methylation of a Silent Controlling Element in the Murine A(vy) Allele Is Incomplete and Unresponsive to Methyl Donor Supplementation
title_full_unstemmed CpG Methylation of a Silent Controlling Element in the Murine A(vy) Allele Is Incomplete and Unresponsive to Methyl Donor Supplementation
title_short CpG Methylation of a Silent Controlling Element in the Murine A(vy) Allele Is Incomplete and Unresponsive to Methyl Donor Supplementation
title_sort cpg methylation of a silent controlling element in the murine a(vy) allele is incomplete and unresponsive to methyl donor supplementation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816220/
https://www.ncbi.nlm.nih.gov/pubmed/20140227
http://dx.doi.org/10.1371/journal.pone.0009055
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