title: Circadian oscillations of protein-coding and regulatory RNAs in a highly dynamic mammalian liver epigenome.
abstract: In the mouse liver, circadian transcriptional rhythms are necessary for metabolic homeostasis. Whether dynamic epigenomic modifications are associated with transcript oscillations has not been systematically investigated. We found that several antisense RNA, lincRNA, and microRNA transcripts also showed circadian oscillations in adult mouse livers. Robust transcript oscillations often correlated with rhythmic histone modifications in promoters, gene bodies, or enhancers, although promoter DNA methylation levels were relatively stable. Such integrative analyses identified oscillating expression of an antisense transcript (asPer2) to the gene encoding the circadian oscillator component Per2. Robust transcript oscillations often accompanied rhythms in multiple histone modifications and recruitment of multiple chromatin-associated clock components. Coupling of cycling histone modifications with nearby oscillating transcripts thus established a temporal relationship between enhancers, genes, and transcripts on a genome-wide scale in a mammalian liver. The results offer a framework for understanding the dynamics of metabolism, circadian clock, and chromatin modifications involved in metabolic homeostasis.
authors.affiliation: Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Vollmers
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schmitz
authors.forename: Jason
authors.initials: J
authors.lastname: Nathanson
authors.forename: Gene
authors.initials: G
authors.lastname: Yeo
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Ecker
authors.forename: Satchidananda
authors.initials: S
authors.lastname: Panda
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000235:genetics*; D019175:DNA Methylation; D057890:Epigenomics; D056426:Genetic Loci; D006657:Histones / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012313:RNA / Q000378:metabolism*; D016372:RNA, Antisense / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D006657:Histones; D035683:MicroRNAs; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D016372:RNA, Antisense; D062085:RNA, Long Noncoding; D012313:RNA