Diet-induced chromatin remodeling in mice livers

The tissue-specific packaging of the genome into the nucleus through chromatin is fundamentally involved in gene regulation, and aberrant modifications to chromatin are a hallmark of many diseases. We show here that a high fat (HF) diet leads to substantial chromatin remodeling in the livers of C57BL/6J mice, as compared to mice fed a control diet. Regions of the genome that display the greatest variation in chromatin accessibility between HF and control regions are targeted by transcription factors with known roles in the liver including HNF4alpha, CEBPalpha, and FOXA1. Whereas livers of DBA/2J mice fed a HF or control diet also demonstrate diet-induced chromatin remodeling, the regions displaying the greatest variation are largely distinct from those observed in B6 livers, indicating a crosstalk between genetic and epigenetic components in determining how diet-induced chromatin remodeling is associated with metabolic disease progression. Examination of chromatin remodeling with FAIRE-seq in livers of mice (C57BL/6J and DBA/2J) fed a high fat or control diet. Complemented with gene expression and H3K4me1 analyses基因组通过染色质在细胞核内的组织特异性包装，从根本上参与基因调控过程，而染色质的异常修饰是多种疾病的标志性特征。本研究证实，相较于喂食对照饮食的小鼠，高脂（HF）饮食可使C57BL/6J小鼠肝脏发生显著的染色质重塑。在高脂与对照饮食组间染色质可及性差异最显著的基因组区域，可被肝脏中已明确功能的转录因子靶向结合，这些因子包括HNF4α、CEBPα与FOXA1。 而喂食高脂或对照饮食的DBA/2J小鼠肝脏同样存在饮食诱导的染色质重塑，但其染色质可及性差异最显著的区域与C57BL/6J小鼠肝脏中的观测结果存在显著差异，这表明遗传与表观遗传组分之间存在串扰，共同调控饮食诱导的染色质重塑与代谢疾病进展之间的关联。 本数据集通过FAIRE-seq技术，对喂食高脂或对照饮食的C57BL/6J与DBA/2J小鼠肝脏组织的染色质重塑情况进行检测，并辅以基因表达及H3K4me1修饰分析。