Leung Amy, Parks Brian W, Du Juan, Trac Candi, Setten Ryan, Chen Yin, Brown Kevin, Lusis Aldons J, Natarajan Rama, Schones Dustin E
From the Departments of Diabetes and.
the Department of Medicine, UCLA, Los Angeles, California 90095.
J Biol Chem. 2014 Aug 22;289(34):23557-67. doi: 10.1074/jbc.M114.581439. Epub 2014 Jul 8.
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.
代谢性疾病由多种遗传和环境因素导致。我们在此报告，环境因素促成代谢性疾病进展的一种方式是通过对染色质的修饰。我们证明，与喂食对照饮食的小鼠相比，高脂饮食会导致C57BL/6J小鼠肝脏中的染色质重塑，并且这些染色质变化与基因表达的变化相关。我们进一步表明，染色质可及性变化最大的区域是肝脏转录因子的作用靶点，包括肝细胞核因子4α（HNF4α）、CCAAT/增强子结合蛋白α（CEBP/α）和叉头框蛋白A1（FOXA1）。在另一种小鼠品系DBA/2J中重复进行染色质和基因表达谱分析，结果显示染色质变化最大的区域在很大程度上具有品系特异性，并且染色质、基因表达和遗传数据的整合可用于表征调控区域。我们的数据表明饮食会导致表观基因组发生显著变化，并证明了染色质重塑中存在品系特异性动态变化。
