title: Chromatin states reveal functional associations for globally defined transcription start sites in four human cell lines.
abstract: BACKGROUND
  Deciphering the most common modes by which chromatin regulates transcription, and how this is related to cellular status and processes is an important task for improving our understanding of human cellular biology. The FANTOM5 and ENCODE projects represent two independent large scale efforts to map regulatory and transcriptional features to the human genome. Here we investigate chromatin features around a comprehensive set of transcription start sites in four cell lines by integrating data from these two projects.
  
  
  RESULTS
  Transcription start sites can be distinguished by chromatin states defined by specific combinations of both chromatin mark enrichment and the profile shapes of these chromatin marks. The observed patterns can be associated with cellular functions and processes, and they also show association with expression level, location relative to nearby genes, and CpG content. In particular we find a substantial number of repressed inter- and intra-genic transcription start sites enriched for active chromatin marks and Pol II, and these sites are strongly associated with immediate-early response processes and cell signaling. Associations between start sites with similar chromatin patterns are validated by significant correlations in their global expression profiles.
  
  
  CONCLUSIONS
  The results confirm the link between chromatin state and cellular function for expressed transcripts, and also indicate that active chromatin states at repressed transcripts may poise transcripts for rapid activation during immune response.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, P,O, Box 8905, NO-7491 Trondheim, Norway. morten.rye@ntnu.no.
authors.forename: Morten
authors.initials: M
authors.lastname: Rye
authors.forename: Geir Kjetil
authors.initials: GK
authors.lastname: Sandve
authors.forename: Carsten O
authors.initials: CO
authors.lastname: Daub
authors.forename: Hideya
authors.initials: H
authors.lastname: Kawaji
authors.forename: Piero
authors.initials: P
authors.lastname: Carninci
authors.forename: Alistair R R
authors.initials: AR
authors.lastname: Forrest
authors.forename: Finn
authors.initials: F
authors.lastname: Drabløs
mesh_terms: D000465:Algorithms; D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D016000:Cluster Analysis; D019295:Computational Biology; D018899:CpG Islands; D005786:Gene Expression Regulation; D015723:Gene Library; D006367:HeLa Cells; D056945:Hep G2 Cells; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D025341:Principal Component Analysis; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism; D024363:Transcription Initiation Site
chemical_list: D002843:Chromatin; D006657:Histones; D014157:Transcription Factors