title: Differential patterns of intronic and exonic DNA regions with respect to RNA polymerase II occupancy, nucleosome density and H3K36me3 marking in fission yeast.
abstract: BACKGROUND
  The generation of mature mRNAs involves interconnected processes, including transcription by RNA polymerase II (Pol II), modification of histones, and processing of pre-mRNAs through capping, intron splicing, and polyadenylation. These processes are thought to be integrated, both spatially and temporally, but it is unclear how these connections manifest at a global level with respect to chromatin patterns and transcription kinetics. We sought to clarify the relationships between chromatin, transcription and splicing using multiple genome-wide approaches in fission yeast.
  
  
  RESULTS
  To investigate these functional interdependencies, we determined Pol II occupancy across all genes using high-density tiling arrays. We also performed ChIP-chip on the same array platform to globally map histone H3 and its H3K36me3 modification, complemented by formaldehyde-assisted isolation of regulatory elements (FAIRE). Surprisingly, Pol II occupancy was higher in introns than in exons, and this difference was inversely correlated with gene expression levels at a global level. Moreover, introns showed distinct distributions of histone H3, H3K36me3 and FAIRE signals, similar to those at promoters and terminators. These distinct transcription and chromatin patterns of intronic regions were most pronounced in poorly expressed genes.
  
  
  CONCLUSIONS
  Our findings suggest that Pol II accumulates at the 3' ends of introns, leading to substantial transcriptional delays in weakly transcribed genes. We propose that the global relationship between transcription, chromatin remodeling, and splicing may reflect differences in local nuclear environments, with highly expressed genes being associated with abundant processing factors that promote effective intron splicing and transcriptional elongation.
authors.affiliation: Department of Genetics, Evolution and Environment and UCL Cancer Institute, University College London, London WC1E 6BT, UK. brian.wilhelm@umontreal.ca
authors.forename: Brian T
authors.initials: BT
authors.lastname: Wilhelm
authors.forename: Samuel
authors.initials: S
authors.lastname: Marguerat
authors.forename: Sofia
authors.initials: S
authors.lastname: Aligianni
authors.forename: Sandra
authors.initials: S
authors.lastname: Codlin
authors.forename: Stephen
authors.initials: S
authors.lastname: Watt
authors.forename: Jürg
authors.initials: J
authors.lastname: Bähler
mesh_terms: D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D004271:DNA, Fungal / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D006657:Histones / Q000235:genetics / Q000378:metabolism; D007438:Introns; D009707:Nucleosomes / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D026723:Polyadenylation / Q000235:genetics; D012319:RNA Polymerase II / Q000235:genetics* / Q000378:metabolism; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D004271:DNA, Fungal; D006657:Histones; D009707:Nucleosomes; D012322:RNA Precursors; D012333:RNA, Messenger; D012319:RNA Polymerase II