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

Authors

Anna L. Tyler, The Jackson LaboratoryFollow
Catrina Spruce, The Jackson LaboratoryFollow
Romy Kursawe, The Jackson LaboratoryFollow
Annat Haber, The Jackson LaboratoryFollow
Robyn L Ball, The Jackson LaboratoryFollow
Wendy A Pitman, The Jackson Laboratory
Alexander D Fine, The Jackson LaboratoryFollow
Narayanan Raghupathy, The Jackson LaboratoryFollow
Michael Walker, The Jackson LaboratoryFollow
Vivek M. Philip, The Jackson LaboratoryFollow
Christopher L. Baker, The Jackson LaboratoryFollow
J Matthew Mahoney, The Jackson LaboratoryFollow
Gary Churchill, The Jackson LaboratoryFollow
Jennifer J. Trowbridge, The Jackson LaboratoryFollow
Michael L. Stitzel, The Jackson LaboratoryFollow
Kenneth Paigen, The Jackson LaboratoryFollow
Petko M. Petkov, The Jackson LaboratoryFollow
Gregory W. Carter, The Jackson LaboratoryFollow

Document Type

Article

Publication Date

6-1-2023

Original Citation

Tyler AL, Spruce C, Kursawe R, Haber A, Ball R, Pitman W, Fine A, Raghupathy N, Walker M, Philip VM, Baker CL, Mahoney J, Churchill G, Trowbridge JJ, Stitzel ML, Paigen K, Petkov PM, Carter GW. Variation in histone configurations correlates with gene expression across nine inbred strains of mice. Genome Res. 2023;33(6):857-71

Keywords

JMG, JGM, SS1, Humans, Mice, Animals, Histones, Promoter Regions, Genetic, DNA Methylation, Chromatin, Epigenesis, Genetic, Histone Code, Mice, Inbred Strains, Gene Expression

JAX Source

Genome Res. 2023;33(6):857-71

ISSN

1549-5469

PMID

37217254

DOI

https://doi.org/10.1101/gr.277467.122

Abstract

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), and DNA methylation. We used ChromHMM to identify 14 chromatin states, each of which represented a distinct combination of the four histone modifications. We found that the epigenetic landscape was highly variable across the DO founders and was 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 chromatin state and DNA methylation in hepatocytes across nine widely used strains of laboratory mice.

Comments

This manuscript is Open Access.This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International license), as described at http://creativecommons.org/licenses/by/4.0/.