title: A genome-wide analysis of open chromatin in human tracheal epithelial cells reveals novel candidate regulatory elements for lung function.
abstract: BACKGROUND
  Distal cell-type-specific regulatory elements may be located at very large distances from the genes that they control and are often hidden within intergenic regions or in introns of other genes. The development of methods that enable mapping of regions of open chromatin genome wide has greatly advanced the identification and characterisation of these elements.
  
  
  METHODS
  Here we use DNase I hypersensitivity mapping followed by deep sequencing (DNase-seq) to generate a map of open chromatin in primary human tracheal epithelial (HTE) cells and use bioinformatic approaches to characterise the distribution of these sites within the genome and with respect to gene promoters, intronic and intergenic regions.
  
  
  RESULTS
  Genes with HTE-selective open chromatin at their promoters were associated with multiple pathways of epithelial function and differentiation. The data predict novel cell-type-specific regulatory elements for genes involved in HTE cell function, such as structural proteins and ion channels, and the transcription factors that may interact with them to control gene expression. Moreover, the map of open chromatin can identify the location of potentially critical regulatory elements in genome-wide association studies (GWAS) in which the strongest association is with single nucleotide polymorphisms in non-coding regions of the genome. We demonstrate its relevance to a recent GWAS that identifies modifiers of cystic fibrosis lung disease severity.
  
  
  CONCLUSIONS
  Since HTE cells have many functional similarities with bronchial epithelial cells and other differentiated cells in the respiratory epithelium, these data are of direct relevance to elucidating the molecular basis of normal lung function and lung disease.
authors.affiliation: Human Molecular Genetics Program, Children's Memorial Research Center, 2300 Children's Plaza, Box 211, Chicago, IL 60614, USA.
authors.forename: Jared M
authors.initials: JM
authors.lastname: Bischof
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ott
authors.forename: Shih-Hsing
authors.initials: SH
authors.lastname: Leir
authors.forename: Nehal
authors.initials: N
authors.lastname: Gosalia
authors.forename: Lingyun
authors.initials: L
authors.lastname: Song
authors.forename: Darin
authors.initials: D
authors.lastname: London
authors.forename: Terrence S
authors.initials: TS
authors.lastname: Furey
authors.forename: Calvin U
authors.initials: CU
authors.lastname: Cotton
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Crawford
authors.forename: Ann
authors.initials: A
authors.lastname: Harris
mesh_terms: D002843:Chromatin / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods; D019295:Computational Biology; D003850:Deoxyribonuclease I; D004847:Epithelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000502:physiology*; D020545:Respiratory Mucosa / Q000378:metabolism*; D014132:Trachea / Q000166:cytology*
chemical_list: D002843:Chromatin; D003850:Deoxyribonuclease I