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论文题目: Long-Range Chromosome Interactions Mediated by Cohesin Shape Circadian Gene Expression
英文论文题目: Long-Range Chromosome Interactions Mediated by Cohesin Shape Circadian Gene Expression
第一作者: Xu, YC; Guo, WM; Li, P; Zhang, Y; Zhao, M; Fan, ZH; Zhao, ZH; Yan, J
英文第一作者: Xu, YC; Guo, WM; Li, P; Zhang, Y; Zhao, M; Fan, ZH; Zhao, ZH; Yan, J
联系作者: Yan, J (reprint author), Chinese Acad Sci, CAS MPG Partner Inst Computat Biol, Shanghai Inst Biol Sci, Shanghai, Peoples R China.
英文联系作者: Yan, J (reprint author), Chinese Acad Sci, CAS MPG Partner Inst Computat Biol, Shanghai Inst Biol Sci, Shanghai, Peoples R China.
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发表年度: 2016
卷: 12
期: 5
页码: e1005992
摘要: Mammalian circadian rhythm is established by the negative feedback loops consisting of a set of clock genes, which lead to the circadian expression of thousands of downstream genes in vivo. As genome-wide transcription is organized under the high-order chromosome structure, it is largely uncharted how circadian gene expression is influenced by chromosome architecture. We focus on the function of chromatin structure proteins cohesin as well as CTCF (CCCTC-binding factor) in circadian rhythm. Using circular chromosome conformation capture sequencing, we systematically examined the interacting loci of a Bmal1-bound super-enhancer upstream of a clock gene Nr1d1 in mouse liver. These interactions are largely stable in the circadian cycle and cohesin binding sites are enriched in the interactome. Global analysis showed that cohesin-CTCF co-binding sites tend to insulate the phases of circadian oscillating genes while cohesin-non-CTCF sites are associated with high circadian rhythmicity of transcription. A model integrating the effects of cohesin and CTCF markedly improved the mechanistic understanding of circadian gene expression. Further experiments in cohesin knockout cells demonstrated that cohesin is required at least in part for driving the circadian gene expression by facilitating the enhancer-promoter looping. This study provided a novel insight into the relationship between circadian transcriptome and the high-order chromosome structure.
英文摘要: Mammalian circadian rhythm is established by the negative feedback loops consisting of a set of clock genes, which lead to the circadian expression of thousands of downstream genes in vivo. As genome-wide transcription is organized under the high-order chromosome structure, it is largely uncharted how circadian gene expression is influenced by chromosome architecture. We focus on the function of chromatin structure proteins cohesin as well as CTCF (CCCTC-binding factor) in circadian rhythm. Using circular chromosome conformation capture sequencing, we systematically examined the interacting loci of a Bmal1-bound super-enhancer upstream of a clock gene Nr1d1 in mouse liver. These interactions are largely stable in the circadian cycle and cohesin binding sites are enriched in the interactome. Global analysis showed that cohesin-CTCF co-binding sites tend to insulate the phases of circadian oscillating genes while cohesin-non-CTCF sites are associated with high circadian rhythmicity of transcription. A model integrating the effects of cohesin and CTCF markedly improved the mechanistic understanding of circadian gene expression. Further experiments in cohesin knockout cells demonstrated that cohesin is required at least in part for driving the circadian gene expression by facilitating the enhancer-promoter looping. This study provided a novel insight into the relationship between circadian transcriptome and the high-order chromosome structure.
刊物名称: PLOS GENETICS
英文刊物名称: PLOS GENETICS
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学科: Genetics & Heredity
英文学科: Genetics & Heredity
影响因子: 6.1
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论文类别: Article
英文论文类别: Article
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