title: Assaying the regulatory potential of mammalian conserved non-coding sequences in human cells.
abstract: BACKGROUND
  Conserved non-coding sequences in the human genome are approximately tenfold more abundant than known genes, and have been hypothesized to mark the locations of cis-regulatory elements. However, the global contribution of conserved non-coding sequences to the transcriptional regulation of human genes is currently unknown. Deeply conserved elements shared between humans and teleost fish predominantly flank genes active during morphogenesis and are enriched for positive transcriptional regulatory elements. However, such deeply conserved elements account for <1% of the conserved non-coding sequences in the human genome, which are predominantly mammalian.
  
  
  RESULTS
  We explored the regulatory potential of a large sample of these 'common' conserved non-coding sequences using a variety of classic assays, including chromatin remodeling, and enhancer/repressor and promoter activity. When tested across diverse human model cell types, we find that the fraction of experimentally active conserved non-coding sequences within any given cell type is low (approximately 5%), and that this proportion increases only modestly when considered collectively across cell types.
  
  
  CONCLUSIONS
  The results suggest that classic assays of cis-regulatory potential are unlikely to expose the functional potential of the substantial majority of mammalian conserved non-coding sequences in the human genome.
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva Medical School, 1 rue Michel Servet, 1211, Geneva 4, Switzerland. Catia.Attanasio@medecine.unige.ch
authors.forename: Catia
authors.initials: C
authors.lastname: Attanasio
authors.forename: Alexandre
authors.initials: A
authors.lastname: Reymond
authors.forename: Richard
authors.initials: R
authors.lastname: Humbert
authors.forename: Robert
authors.initials: R
authors.lastname: Lyle
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kuehn
authors.forename: Shane
authors.initials: S
authors.lastname: Neph
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sabo
authors.forename: Jeff
authors.initials: J
authors.lastname: Goldy
authors.forename: Molly
authors.initials: M
authors.lastname: Weaver
authors.forename: Andrew
authors.initials: A
authors.lastname: Haydock
authors.forename: Kristin
authors.initials: K
authors.lastname: Lee
authors.forename: Michael
authors.initials: M
authors.lastname: Dorschner
authors.forename: Emmanouil T
authors.initials: ET
authors.lastname: Dermitzakis
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Antonarakis
authors.forename: John A
authors.initials: JA
authors.lastname: Stamatoyannopoulos
mesh_terms: D000818:Animals; D002460:Cell Line; D017124:Conserved Sequence / Q000235:genetics*; D019143:Evolution, Molecular; D016678:Genome; D015894:Genome, Human; D006801:Humans; D051379:Mice; D012045:Regulatory Sequences, Nucleic Acid