title: DNase I-hypersensitive exons colocalize with promoters and distal regulatory elements.
abstract: The precise splicing of genes confers an enormous transcriptional complexity to the human genome. The majority of gene splicing occurs cotranscriptionally, permitting epigenetic modifications to affect splicing outcomes. Here we show that select exonic regions are demarcated within the three-dimensional structure of the human genome. We identify a subset of exons that exhibit DNase I hypersensitivity and are accompanied by 'phantom' signals in chromatin immunoprecipitation and sequencing (ChIP-seq) that result from cross-linking with proximal promoter- or enhancer-bound factors. The capture of structural features by ChIP-seq is confirmed by chromatin interaction analysis that resolves local intragenic loops that fold exons close to cognate promoters while excluding intervening intronic sequences. These interactions of exons with promoters and enhancers are enriched for alternative splicing events, an effect reflected in cell type-specific periexonic DNase I hypersensitivity patterns. Collectively, our results connect local genome topography, chromatin structure and cis-regulatory landscapes with the generation of human transcriptional complexity by cotranscriptional splicing.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland, Australia.
authors.forename: Tim R
authors.initials: TR
authors.lastname: Mercer
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Edwards
authors.forename: Michael B
authors.initials: MB
authors.lastname: Clark
authors.forename: Shane J
authors.initials: SJ
authors.lastname: Neph
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Stergachis
authors.forename: Sam
authors.initials: S
authors.lastname: John
authors.forename: Richard
authors.initials: R
authors.lastname: Sandstrom
authors.forename: Guoliang
authors.initials: G
authors.lastname: Li
authors.forename: Kuljeet S
authors.initials: KS
authors.lastname: Sandhu
authors.forename: Yijun
authors.initials: Y
authors.lastname: Ruan
authors.forename: Lars K
authors.initials: LK
authors.lastname: Nielsen
authors.forename: John S
authors.initials: JS
authors.lastname: Mattick
authors.forename: John A
authors.initials: JA
authors.lastname: Stamatoyannopoulos
mesh_terms: D017398:Alternative Splicing; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology; D030561:Databases, Nucleic Acid; D003850:Deoxyribonuclease I / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005091:Exons; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009690:Nucleic Acid Conformation; D009928:Organ Specificity / Q000235:genetics; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid
chemical_list: D003850:Deoxyribonuclease I