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Broad Epigenetic Signature of Maternal Care in the Brain of Adult Rats

BACKGROUND: Maternal care is associated with long-term effects on behavior and epigenetic programming of the NR3C1 (GLUCOCORTICOID RECEPTOR) gene in the hippocampus of both rats and humans. In the rat, these effects are reversed by cross-fostering, demonstrating that they are defined by epigenetic r...

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Autores principales: McGowan, Patrick O., Suderman, Matthew, Sasaki, Aya, Huang, Tony C. T., Hallett, Michael, Meaney, Michael J., Szyf, Moshe
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046141/
https://www.ncbi.nlm.nih.gov/pubmed/21386994
http://dx.doi.org/10.1371/journal.pone.0014739
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author McGowan, Patrick O.
Suderman, Matthew
Sasaki, Aya
Huang, Tony C. T.
Hallett, Michael
Meaney, Michael J.
Szyf, Moshe
author_facet McGowan, Patrick O.
Suderman, Matthew
Sasaki, Aya
Huang, Tony C. T.
Hallett, Michael
Meaney, Michael J.
Szyf, Moshe
author_sort McGowan, Patrick O.
collection PubMed
description BACKGROUND: Maternal care is associated with long-term effects on behavior and epigenetic programming of the NR3C1 (GLUCOCORTICOID RECEPTOR) gene in the hippocampus of both rats and humans. In the rat, these effects are reversed by cross-fostering, demonstrating that they are defined by epigenetic rather than genetic processes. However, epigenetic changes at a single gene promoter are unlikely to account for the range of outcomes and the persistent change in expression of hundreds of additional genes in adult rats in response to differences in maternal care. METHODOLOGY/PRINCIPAL FINDINGS: We examine here using high-density oligonucleotide array the state of DNA methylation, histone acetylation and gene expression in a 7 million base pair region of chromosome 18 containing the NR3C1 gene in the hippocampus of adult rats. Natural variations in maternal care are associated with coordinate epigenetic changes spanning over a hundred kilobase pairs. The adult offspring of high compared to low maternal care mothers show epigenetic changes in promoters, exons, and gene ends associated with higher transcriptional activity across many genes within the locus examined. Other genes in this region remain unchanged, indicating a clustered yet specific and patterned response. Interestingly, the chromosomal region containing the protocadherin-α, -β, and -γ (Pcdh) gene families implicated in synaptogenesis show the highest differential response to maternal care. CONCLUSIONS/SIGNIFICANCE: The results suggest for the first time that the epigenetic response to maternal care is coordinated in clusters across broad genomic areas. The data indicate that the epigenetic response to maternal care involves not only single candidate gene promoters but includes transcriptional and intragenic sequences, as well as those residing distantly from transcription start sites. These epigenetic and transcriptional profiles constitute the first tiling microarray data set exploring the relationship between epigenetic modifications and RNA expression in both protein coding and non-coding regions across a chromosomal locus in the mammalian brain.
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spelling pubmed-30461412011-03-08 Broad Epigenetic Signature of Maternal Care in the Brain of Adult Rats McGowan, Patrick O. Suderman, Matthew Sasaki, Aya Huang, Tony C. T. Hallett, Michael Meaney, Michael J. Szyf, Moshe PLoS One Research Article BACKGROUND: Maternal care is associated with long-term effects on behavior and epigenetic programming of the NR3C1 (GLUCOCORTICOID RECEPTOR) gene in the hippocampus of both rats and humans. In the rat, these effects are reversed by cross-fostering, demonstrating that they are defined by epigenetic rather than genetic processes. However, epigenetic changes at a single gene promoter are unlikely to account for the range of outcomes and the persistent change in expression of hundreds of additional genes in adult rats in response to differences in maternal care. METHODOLOGY/PRINCIPAL FINDINGS: We examine here using high-density oligonucleotide array the state of DNA methylation, histone acetylation and gene expression in a 7 million base pair region of chromosome 18 containing the NR3C1 gene in the hippocampus of adult rats. Natural variations in maternal care are associated with coordinate epigenetic changes spanning over a hundred kilobase pairs. The adult offspring of high compared to low maternal care mothers show epigenetic changes in promoters, exons, and gene ends associated with higher transcriptional activity across many genes within the locus examined. Other genes in this region remain unchanged, indicating a clustered yet specific and patterned response. Interestingly, the chromosomal region containing the protocadherin-α, -β, and -γ (Pcdh) gene families implicated in synaptogenesis show the highest differential response to maternal care. CONCLUSIONS/SIGNIFICANCE: The results suggest for the first time that the epigenetic response to maternal care is coordinated in clusters across broad genomic areas. The data indicate that the epigenetic response to maternal care involves not only single candidate gene promoters but includes transcriptional and intragenic sequences, as well as those residing distantly from transcription start sites. These epigenetic and transcriptional profiles constitute the first tiling microarray data set exploring the relationship between epigenetic modifications and RNA expression in both protein coding and non-coding regions across a chromosomal locus in the mammalian brain. Public Library of Science 2011-02-28 /pmc/articles/PMC3046141/ /pubmed/21386994 http://dx.doi.org/10.1371/journal.pone.0014739 Text en McGowan 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
McGowan, Patrick O.
Suderman, Matthew
Sasaki, Aya
Huang, Tony C. T.
Hallett, Michael
Meaney, Michael J.
Szyf, Moshe
Broad Epigenetic Signature of Maternal Care in the Brain of Adult Rats
title Broad Epigenetic Signature of Maternal Care in the Brain of Adult Rats
title_full Broad Epigenetic Signature of Maternal Care in the Brain of Adult Rats
title_fullStr Broad Epigenetic Signature of Maternal Care in the Brain of Adult Rats
title_full_unstemmed Broad Epigenetic Signature of Maternal Care in the Brain of Adult Rats
title_short Broad Epigenetic Signature of Maternal Care in the Brain of Adult Rats
title_sort broad epigenetic signature of maternal care in the brain of adult rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046141/
https://www.ncbi.nlm.nih.gov/pubmed/21386994
http://dx.doi.org/10.1371/journal.pone.0014739
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