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Variation in histone configurations correlates with gene expression across nine inbred strains of mice

The Diversity Outbred (DO) mice and their inbred founders are widely used models of human disease. However, although the genetic diversity of these mice has been well documented, their epigenetic diversity has not. Epigenetic modifications, such as histone modifications and DNA methylation, are impo...

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Autores principales: Tyler, Anna L., Spruce, Catrina, Kursawe, Romy, Haber, Annat, Ball, Robyn L., Pitman, Wendy A., Fine, Alexander D., Raghupathy, Narayanan, Walker, Michael, Philip, Vivek M., Baker, Christopher L., Mahoney, J. Matthew, Churchill, Gary A., Trowbridge, Jennifer J., Stitzel, Michael L., Paigen, Kenneth, Petkov, Petko M., Carter, Gregory W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10519406/
https://www.ncbi.nlm.nih.gov/pubmed/37217254
http://dx.doi.org/10.1101/gr.277467.122
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author Tyler, Anna L.
Spruce, Catrina
Kursawe, Romy
Haber, Annat
Ball, Robyn L.
Pitman, Wendy A.
Fine, Alexander D.
Raghupathy, Narayanan
Walker, Michael
Philip, Vivek M.
Baker, Christopher L.
Mahoney, J. Matthew
Churchill, Gary A.
Trowbridge, Jennifer J.
Stitzel, Michael L.
Paigen, Kenneth
Petkov, Petko M.
Carter, Gregory W.
author_facet Tyler, Anna L.
Spruce, Catrina
Kursawe, Romy
Haber, Annat
Ball, Robyn L.
Pitman, Wendy A.
Fine, Alexander D.
Raghupathy, Narayanan
Walker, Michael
Philip, Vivek M.
Baker, Christopher L.
Mahoney, J. Matthew
Churchill, Gary A.
Trowbridge, Jennifer J.
Stitzel, Michael L.
Paigen, Kenneth
Petkov, Petko M.
Carter, Gregory W.
author_sort Tyler, Anna L.
collection PubMed
description The Diversity Outbred (DO) mice and their inbred founders are widely used models of human disease. However, although the genetic diversity of these mice has been well documented, their epigenetic diversity has not. Epigenetic modifications, such as histone modifications and DNA methylation, are important regulators of gene expression and, as such, are a critical mechanistic link between genotype and phenotype. Therefore, creating a map of epigenetic modifications in the DO mice and their founders is an important step toward understanding mechanisms of gene regulation and the link to disease in this widely used resource. To this end, we performed a strain survey of epigenetic modifications in hepatocytes of the DO founders. We surveyed four histone modifications (H3K4me1, H3K4me3, H3K27me3, and H3K27ac), as well as DNA methylation. We used ChromHMM to identify 14 chromatin states, each of which represents a distinct combination of the four histone modifications. We found that the epigenetic landscape is highly variable across the DO founders and is associated with variation in gene expression across strains. We found that epigenetic state imputed into a population of DO mice recapitulated the association with gene expression seen in the founders, suggesting that both histone modifications and DNA methylation are highly heritable mechanisms of gene expression regulation. We illustrate how DO gene expression can be aligned with inbred epigenetic states to identify putative cis-regulatory regions. Finally, we provide a data resource that documents strain-specific variation in the chromatin state and DNA methylation in hepatocytes across nine widely used strains of laboratory mice.
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spelling pubmed-105194062023-09-26 Variation in histone configurations correlates with gene expression across nine inbred strains of mice Tyler, Anna L. Spruce, Catrina Kursawe, Romy Haber, Annat Ball, Robyn L. Pitman, Wendy A. Fine, Alexander D. Raghupathy, Narayanan Walker, Michael Philip, Vivek M. Baker, Christopher L. Mahoney, J. Matthew Churchill, Gary A. Trowbridge, Jennifer J. Stitzel, Michael L. Paigen, Kenneth Petkov, Petko M. Carter, Gregory W. Genome Res Research The Diversity Outbred (DO) mice and their inbred founders are widely used models of human disease. However, although the genetic diversity of these mice has been well documented, their epigenetic diversity has not. Epigenetic modifications, such as histone modifications and DNA methylation, are important regulators of gene expression and, as such, are a critical mechanistic link between genotype and phenotype. Therefore, creating a map of epigenetic modifications in the DO mice and their founders is an important step toward understanding mechanisms of gene regulation and the link to disease in this widely used resource. To this end, we performed a strain survey of epigenetic modifications in hepatocytes of the DO founders. We surveyed four histone modifications (H3K4me1, H3K4me3, H3K27me3, and H3K27ac), as well as DNA methylation. We used ChromHMM to identify 14 chromatin states, each of which represents a distinct combination of the four histone modifications. We found that the epigenetic landscape is highly variable across the DO founders and is associated with variation in gene expression across strains. We found that epigenetic state imputed into a population of DO mice recapitulated the association with gene expression seen in the founders, suggesting that both histone modifications and DNA methylation are highly heritable mechanisms of gene expression regulation. We illustrate how DO gene expression can be aligned with inbred epigenetic states to identify putative cis-regulatory regions. Finally, we provide a data resource that documents strain-specific variation in the chromatin state and DNA methylation in hepatocytes across nine widely used strains of laboratory mice. Cold Spring Harbor Laboratory Press 2023-06 /pmc/articles/PMC10519406/ /pubmed/37217254 http://dx.doi.org/10.1101/gr.277467.122 Text en © 2023 Tyler et al.; Published by Cold Spring Harbor Laboratory Press https://creativecommons.org/licenses/by/4.0/This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research
Tyler, Anna L.
Spruce, Catrina
Kursawe, Romy
Haber, Annat
Ball, Robyn L.
Pitman, Wendy A.
Fine, Alexander D.
Raghupathy, Narayanan
Walker, Michael
Philip, Vivek M.
Baker, Christopher L.
Mahoney, J. Matthew
Churchill, Gary A.
Trowbridge, Jennifer J.
Stitzel, Michael L.
Paigen, Kenneth
Petkov, Petko M.
Carter, Gregory W.
Variation in histone configurations correlates with gene expression across nine inbred strains of mice
title Variation in histone configurations correlates with gene expression across nine inbred strains of mice
title_full Variation in histone configurations correlates with gene expression across nine inbred strains of mice
title_fullStr Variation in histone configurations correlates with gene expression across nine inbred strains of mice
title_full_unstemmed Variation in histone configurations correlates with gene expression across nine inbred strains of mice
title_short Variation in histone configurations correlates with gene expression across nine inbred strains of mice
title_sort variation in histone configurations correlates with gene expression across nine inbred strains of mice
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10519406/
https://www.ncbi.nlm.nih.gov/pubmed/37217254
http://dx.doi.org/10.1101/gr.277467.122
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