Gene and genome parameters of mammalian liver circadian genes (LCGs)

PLoS One. 2012;7(10):e46961. doi: 10.1371/journal.pone.0046961. Epub 2012 Oct 10.

Abstract

The mammalian circadian system controls various physiology processes and behavior responses by regulating thousands of circadian genes with rhythmic expressions. In this study, we redefined circadian-regulated genes based on published results in the mouse liver and compared them with other gene groups defined relative to circadian regulations, especially the non-circadian-regulated genes expressed in liver at multiple molecular levels from gene position to protein expression based on integrative analyses of different datasets from the literature. Based on the intra-tissue analysis, the liver circadian genes or LCGs show unique features when compared to other gene groups. First, LCGs in general have less neighboring genes and larger in both genomic and 3'-UTR lengths but shorter in CDS (coding sequence) lengths. Second, LCGs have higher mRNA and protein abundance, higher temporal expression variations, and shorter mRNA half-life. Third, more than 60% of LCGs form major co-expression clusters centered in four temporal windows: dawn, day, dusk, and night. In addition, larger and smaller LCGs are found mainly expressed in the day and night temporal windows, respectively, and we believe that LCGs are well-partitioned into the gene expression regulatory network that takes advantage of gene size, expression constraint, and chromosomal architecture. Based on inter-tissue analysis, more than half of LCGs are ubiquitously expressed in multiple tissues but only show rhythmical expression in one or limited number of tissues. LCGs show at least three-fold lower expression variations across the temporal windows than those among different tissues, and this observation suggests that temporal expression variations regulated by the circadian system is relatively subtle as compared with the tissue expression variations formed during development. Taken together, we suggest that the circadian system selects gene parameters in a cost effective way to improve tissue-specific functions by adapting temporal variations from the environment over evolutionary time scales.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromosome Mapping
  • Chromosomes, Mammalian / genetics
  • Circadian Rhythm / genetics*
  • Cluster Analysis
  • Databases, Genetic
  • Female
  • Gene Expression Profiling*
  • Genomics*
  • Liver / metabolism*
  • Male
  • Mice
  • NIH 3T3 Cells
  • Oligonucleotide Array Sequence Analysis
  • Pituitary Gland / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Grants and funding

This work is supported by grants from the National Basic Research Program (973 Program; 2011CB944100 and 2011CB944101), National Natural Science Foundation of China (90919024), from the Special Foundation Work Program, the Ministry of Science and Technology (2009FY120100), from National Programs for High Technology Research and Development (863 Program), the Ministry of Science and Technology of the People's Republic of China (2012AA020409). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.