Open Chromatin Profiling in Mice Livers Reveals Unique Chromatin Variations Induced by High Fat Diet*
- Amy Leung‡,
- Brian W. Parks§,
- Juan Du¶,‖,
- Candi Trac¶,
- Ryan Setten‖,
- Yin Chen‖,
- Kevin Brown¶,
- Aldons J. Lusis§,
- Rama Natarajan‡,‖1 and
- Dustin E. Schones¶,‖2
- From the Departments of ‡Diabetes and
- ¶Cancer Biology, Beckman Research Institute and
- the ‖Irell & Manella Graduate School of Biological Sciences, City of Hope, Duarte, California 91010 and
- the §Department of Medicine, UCLA, Los Angeles, California 90095
- ↵1 To whom correspondence may be addressed: Dept. of Diabetes, Beckman Research Institute, City of Hope, 1500 E. Duarte Rd., Duarte, CA 91016. Tel.: 626-256-4673 (ext. 62289); E-mail: rnatarajan{at}coh.org.
- ↵2 To whom correspondence may be addressed: Dept. of Cancer Biology, Beckman Research Institute, City of Hope, 1500 E. Duarte Rd., Duarte, CA 91016. Tel.: 626-471-9319; E-mail: dschones{at}coh.org.
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.
Footnotes
-
↵* This work was supported by Schaeffer endowment funds and National Institutes of Health Grants K22HL101950 (to D. E. S.), T32DK007571-24 (to A. L.), R01HL106089, R01HL087864, and RO1DK065073 (to R. N.), and HL28482 and DK094311 (to A. J. L.).
-
All sequencing datasets presented in this paper have been deposited into the NCBI GEO repository under accession number GSE55581.
- Received May 16, 2014.
- Revision received July 1, 2014.
- © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
