title: Conservation and implications of eukaryote transcriptional regulatory regions across multiple species.
abstract: BACKGROUND
  Increasing evidence shows that whole genomes of eukaryotes are almost entirely transcribed into both protein coding genes and an enormous number of non-protein-coding RNAs (ncRNAs). Therefore, revealing the underlying regulatory mechanisms of transcripts becomes imperative. However, for a complete understanding of transcriptional regulatory mechanisms, we need to identify the regions in which they are found. We will call these transcriptional regulation regions, or TRRs, which can be considered functional regions containing a cluster of regulatory elements that cooperatively recruit transcriptional factors for binding and then regulating the expression of transcripts.
  
  
  RESULTS
  We constructed a hierarchical stochastic language (HSL) model for the identification of core TRRs in yeast based on regulatory cooperation among TRR elements. The HSL model trained based on yeast achieved comparable accuracy in predicting TRRs in other species, e.g., fruit fly, human, and rice, thus demonstrating the conservation of TRRs across species. The HSL model was also used to identify the TRRs of genes, such as p53 or OsALYL1, as well as microRNAs. In addition, the ENCODE regions were examined by HSL, and TRRs were found to pervasively locate in the genomes.
  
  
  CONCLUSIONS
  Our findings indicate that 1) the HSL model can be used to accurately predict core TRRs of transcripts across species and 2) identified core TRRs by HSL are proper candidates for the further scrutiny of specific regulatory elements and mechanisms. Meanwhile, the regulatory activity taking place in the abundant numbers of ncRNAs might account for the ubiquitous presence of TRRs across the genome. In addition, we also found that the TRRs of protein coding genes and ncRNAs are similar in structure, with the latter being more conserved than the former.
authors.affiliation: School of Mathematical Sciences, Peking University, Beijing, PR China. wanlin@ctb.pku.edu.cn
authors.forename: Lin
authors.initials: L
authors.lastname: Wan
authors.forename: Dayong
authors.initials: D
authors.lastname: Li
authors.forename: Donglei
authors.initials: D
authors.lastname: Zhang
authors.forename: Xue
authors.initials: X
authors.lastname: Liu
authors.forename: Wenjiang J
authors.initials: WJ
authors.lastname: Fu
authors.forename: Lihuang
authors.initials: L
authors.lastname: Zhu
authors.forename: Minghua
authors.initials: M
authors.lastname: Deng
authors.forename: Fengzhu
authors.initials: F
authors.lastname: Sun
authors.forename: Minping
authors.initials: M
authors.lastname: Qian
mesh_terms: D000818:Animals; D017124:Conserved Sequence / Q000235:genetics; D005057:Eukaryotic Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D016681:Genome, Fungal; D006801:Humans; D022661:RNA, Untranslated / Q000235:genetics; D050436:Regulatory Elements, Transcriptional; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D013045:Species Specificity; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D022661:RNA, Untranslated; D016159:Tumor Suppressor Protein p53