title: Open chromatin profiling in mice livers reveals unique chromatin variations induced by high fat diet.
abstract: Metabolic diseases result from multiple genetic and environmental factors. We report here that one manner in which environmental factors can contribute to metabolic disease progression is through modification to chromatin. We demonstrate that high fat diet leads to chromatin remodeling in the livers of C57BL/6J mice, as compared with mice fed a control diet, and that these chromatin changes are associated with changes in gene expression. We further show that the regions of greatest variation in chromatin accessibility are targeted by liver transcription factors, including HNF4α, CCAAT/enhancer-binding protein α (CEBP/α), and FOXA1. Repeating the chromatin and gene expression profiling in another mouse strain, DBA/2J, revealed that the regions of greatest chromatin change are largely strain-specific and that integration of chromatin, gene expression, and genetic data can be used to characterize regulatory regions. Our data indicate dramatic changes in the epigenome due to diet and demonstrate strain-specific dynamics in chromatin remodeling.
authors.affiliation: From the Departments of Diabetes and.
authors.forename: Amy
authors.initials: A
authors.lastname: Leung
authors.affiliation: the Department of Medicine, UCLA, Los Angeles, California 90095.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Parks
authors.affiliation: Cancer Biology, Beckman Research Institute and the Irell & Manella Graduate School of Biological Sciences, City of Hope, Duarte, California 91010 and.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.affiliation: Cancer Biology, Beckman Research Institute and.
authors.forename: Candi
authors.initials: C
authors.lastname: Trac
authors.affiliation: the Irell & Manella Graduate School of Biological Sciences, City of Hope, Duarte, California 91010 and.
authors.forename: Ryan
authors.initials: R
authors.lastname: Setten
authors.affiliation: the Irell & Manella Graduate School of Biological Sciences, City of Hope, Duarte, California 91010 and.
authors.forename: Yin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Cancer Biology, Beckman Research Institute and.
authors.forename: Kevin
authors.initials: K
authors.lastname: Brown
authors.affiliation: the Department of Medicine, UCLA, Los Angeles, California 90095.
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
authors.affiliation: From the Departments of Diabetes and the Irell & Manella Graduate School of Biological Sciences, City of Hope, Duarte, California 91010 and rnatarajan@coh.org.
authors.forename: Rama
authors.initials: R
authors.lastname: Natarajan
authors.affiliation: Cancer Biology, Beckman Research Institute and the Irell & Manella Graduate School of Biological Sciences, City of Hope, Duarte, California 91010 and dschones@coh.org.
authors.forename: Dustin E
authors.initials: DE
authors.lastname: Schones
mesh_terms: D000818:Animals; D001483:Base Sequence; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers; D059305:Diet, High-Fat; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D040641:Quantitative Trait Loci
chemical_list: D002843:Chromatin; D017931:DNA Primers
keywords: Chromatin; Diet; Gene Regulation; Gene-environment Interaction; Liver Metabolism; Metabolic Disease