A class of circadian long non-coding RNAs mark enhancers modulating long-range circadian gene regulation
Autor: | Ping Li, Haifang Wang, Parth Devesh Joshi, Yichi Xu, Meng Zhao, Zhihu Zhao, Zenghua Fan, Weimin Guo, Yan Zhang, Jun Yan |
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Rok vydání: | 2017 |
Předmět: |
Male
0301 basic medicine Circadian clock Biology RAR-related orphan receptor alpha Mice 03 medical and health sciences Genetics Animals Circadian rhythm Enhancer Transcription factor Gene Cell Nucleus Regulation of gene expression Binding Sites Gene Expression Profiling Gene regulation Chromatin and Epigenetics ARNTL Transcription Factors Circadian Rhythm Rats Mice Inbred C57BL Gene expression profiling Enhancer Elements Genetic 030104 developmental biology Gene Expression Regulation Liver Genetic Loci Nuclear Receptor Subfamily 1 Group D Member 1 RNA Long Noncoding Transcriptome Protein Binding |
Zdroj: | Nucleic Acids Research |
ISSN: | 1362-4962 0305-1048 |
DOI: | 10.1093/nar/gkx156 |
Popis: | Circadian rhythm exerts its influence on animal physiology and behavior by regulating gene expression at various levels. Here we systematically explored circadian long non-coding RNAs (lncRNAs) in mouse liver and examined their circadian regulation. We found that a significant proportion of circadian lncRNAs are expressed at enhancer regions, mostly bound by two key circadian transcription factors, BMAL1 and REV-ERBα. These circadian lncRNAs showed similar circadian phases with their nearby genes. The extent of their nuclear localization is higher than protein coding genes but less than enhancer RNAs. The association between enhancer and circadian lncRNAs is also observed in tissues other than liver. Comparative analysis between mouse and rat circadian liver transcriptomes showed that circadian transcription at lncRNA loci tends to be conserved despite of low sequence conservation of lncRNAs. One such circadian lncRNA termed lnc-Crot led us to identify a super-enhancer region interacting with a cluster of genes involved in circadian regulation of metabolism through long-range interactions. Further experiments showed that lnc-Crot locus has enhancer function independent of lnc-Crot's transcription. Our results suggest that the enhancer-associated circadian lncRNAs mark the genomic loci modulating long-range circadian gene regulation and shed new lights on the evolutionary origin of lncRNAs. |
Databáze: | OpenAIRE |
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