Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Department of Genetics, and The Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Department of Genetics, and The Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell. 2014 Nov 20;159(5):1140-1152. doi: 10.1016/j.cell.2014.10.022.
Mammalian transcriptomes display complex circadian rhythms with multiple phases of gene expression that cannot be accounted for by current models of the molecular clock. We have determined the underlying mechanisms by measuring nascent RNA transcription around the clock in mouse liver. Unbiased examination of enhancer RNAs (eRNAs) that cluster in specific circadian phases identified functional enhancers driven by distinct transcription factors (TFs). We further identify on a global scale the components of the TF cistromes that function to orchestrate circadian gene expression. Integrated genomic analyses also revealed mechanisms by which a single circadian factor controls opposing transcriptional phases. These findings shed light on the diversity and specificity of TF function in the generation of multiple phases of circadian gene transcription in a mammalian organ.
哺乳动物转录组显示出复杂的昼夜节律,其基因表达具有多个相位,这不能用当前的分子钟模型来解释。我们通过在小鼠肝脏中进行昼夜转录本的测量,确定了潜在的机制。对特定昼夜相位聚集的增强子 RNA (eRNA)进行无偏分析,鉴定了由不同转录因子 (TF) 驱动的功能增强子。我们进一步在全局范围内确定了 TF 顺式作用元件的组成部分,这些元件的功能是协调昼夜基因表达。综合基因组分析还揭示了单个昼夜节律因子控制相反转录相位的机制。这些发现揭示了在哺乳动物器官中产生多个昼夜基因转录相位时,TF 功能的多样性和特异性。