DNase I-hypersensitive exons colocalize with promoters and distal regulatory elements

Mercer, Tim R., Edwards, Stacey L., Clark, Michael B., Neph, Shane J., Wang, Hao, Stergachis, Andrew B., John, Sam, Sandstrom, Richard, Li, Guoliang, Sandhu, Kuljeet S., Ruan, Yijun, Nielsen, Lars K., Mattick, John S. and Stamatoyannopoulos, John A. (2013) DNase I-hypersensitive exons colocalize with promoters and distal regulatory elements. Nature Genetics, 45 8: 852-859. doi:10.1038/ng.2677

Author Mercer, Tim R.
Edwards, Stacey L.
Clark, Michael B.
Neph, Shane J.
Wang, Hao
Stergachis, Andrew B.
John, Sam
Sandstrom, Richard
Li, Guoliang
Sandhu, Kuljeet S.
Ruan, Yijun
Nielsen, Lars K.
Mattick, John S.
Stamatoyannopoulos, John A.
Title DNase I-hypersensitive exons colocalize with promoters and distal regulatory elements
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1061-4036
Publication date 2013-08
Sub-type Article (original research)
DOI 10.1038/ng.2677
Volume 45
Issue 8
Start page 852
End page 859
Total pages 8
Place of publication New York, NY United States
Publisher Nature Publishing Group
Collection year 2014
Language eng
Formatted 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.
Keyword Subcellular RNA fractions
Transcription factories
Human genome
Chromatin interactome
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

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