title: Long-Range Chromosome Interactions Mediated by Cohesin Shape Circadian Gene Expression.
abstract: 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.
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|University of Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yichi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Guo
authors.affiliation: Beijing Institute of Biotechnology, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Beijing Institute of Biotechnology, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhao
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|University of Chinese Academy of Sciences, Shanghai, China.
authors.forename: Zenghua
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Beijing Institute of Biotechnology, Beijing, China.
authors.forename: Zhihu
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D002875:Chromosomes / Q000235:genetics; D002940:Circadian Rhythm / Q000235:genetics*; D025461:Feedback, Physiological; D051268:GA-Binding Protein Transcription Factor / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D000097722:Cohesins
chemical_list: D056930:ARNTL Transcription Factors; D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D051268:GA-Binding Protein Transcription Factor; D009687:Nuclear Proteins; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D012097:Repressor Proteins; D000097722:Cohesins; C538961:Bmal1 protein, mouse; C000619698:Ctcf protein, mouse; C495656:Gabpa protein, mouse; C498262:Nr1d1 protein, mouse; C556316:RAD21L protein, mouse; C476538:Stag2 protein, mouse