title: Map of open and closed chromatin domains in Drosophila genome.
abstract: BACKGROUND
  Chromatin compactness has been considered a major determinant of gene activity and has been associated with specific chromatin modifications in studies on a few individual genetic loci. At the same time, genome-wide patterns of open and closed chromatin have been understudied, and are at present largely predicted from chromatin modification and gene expression data. However the universal applicability of such predictions is not self-evident, and requires experimental verification.
  
  
  RESULTS
  We developed and implemented a high-throughput analysis for general chromatin sensitivity to DNase I which provides a comprehensive epigenomic assessment in a single assay. Contiguous domains of open and closed chromatin were identified by computational analysis of the data, and correlated to other genome annotations including predicted chromatin "states", individual chromatin modifications, nuclear lamina interactions, and gene expression. While showing that the widely trusted predictions of chromatin structure are correct in the majority of cases, we detected diverse "exceptions" from the conventional rules. We found a profound paucity of chromatin modifications in a major fraction of closed chromatin, and identified a number of loci where chromatin configuration is opposite to that expected from modification and gene expression patterns. Further, we observed that chromatin of large introns tends to be closed even when the genes are expressed, and that a significant proportion of active genes including their promoters are located in closed chromatin.
  
  
  CONCLUSIONS
  These findings reveal limitations of the existing predictive models, indicate novel mechanisms of epigenetic regulation, and provide important insights into genome organization and function.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Milon
authors.forename: Yezhou
authors.initials: Y
authors.lastname: Sun
authors.forename: Weizhong
authors.initials: W
authors.lastname: Chang
authors.forename: Todd
authors.initials: T
authors.lastname: Creasy
authors.forename: Anup
authors.initials: A
authors.lastname: Mahurkar
authors.forename: Amol
authors.initials: A
authors.lastname: Shetty
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, 108 N, Greene St,, Baltimore, MD 21201, USA. dnurminsky@som.umaryland.edu.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Nurminsky
authors.forename: Maria
authors.initials: M
authors.lastname: Nurminskaya
mesh_terms: D000818:Animals; D001665:Binding Sites; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D002874:Chromosome Mapping; D019295:Computational Biology / Q000379:methods; D003850:Deoxyribonuclease I / Q000378:metabolism; D004330:Drosophila / Q000235:genetics*; D049750:Genome, Insect; D011485:Protein Binding
chemical_list: D002843:Chromatin; D003850:Deoxyribonuclease I