Discovery of active enhancers through bidirectional expression of short transcripts

Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Genome biology (Impact Factor: 10.47). 11/2011; 12(11):R113. DOI: 10.1186/gb-2011-12-11-r113
Source: PubMed

ABSTRACT Long-range regulatory elements, such as enhancers, exert substantial control over tissue-specific gene expression patterns. Genome-wide discovery of functional enhancers in different cell types is important for our understanding of genome function as well as human disease etiology.
In this study, we developed an in silico approach to model the previously reported phenomenon of transcriptional pausing, accompanied by divergent transcription, at active promoters. We then used this model for large-scale prediction of non-promoter-associated bidirectional expression of short transcripts. Our predictions were significantly enriched for DNase hypersensitive sites, histone H3 lysine 27 acetylation (H3K27ac), and other chromatin marks associated with active rather than poised or repressed enhancers. We also detected modest bidirectional expression at binding sites of the CCCTC-factor (CTCF) genome-wide, particularly those that overlap H3K27ac.
Our findings indicate that the signature of bidirectional expression of short transcripts, learned from promoter-proximal transcriptional pausing, can be used to predict active long-range regulatory elements genome-wide, likely due in part to specific association of RNA polymerase with enhancer regions.

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Available from: Michael Melgar, Aug 03, 2015
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    • "The global identification of transcription start sites will facilitate future studies of gene expression regulation in C. elegans and allow comparative analyses with other eukaryotes. Mammalian enhancer regions have also been shown to be transcribed, but this phenomenon is not well-characterized, and its function is not yet known (De Santa et al. 2010; Kim et al. 2010; Koch et al. 2011; Melgar et al. 2011; Wang et al. 2011; Natoli and Andrau 2012). In addition, both unidirectional and bidirectional transcription has been observed. "
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    • "Alternative mechanisms for enhancer function have also been proposed. Recent genome-wide studies have made clear that RNA pol II is recruited to enhancers (De Santa et al., 2010; Kim et al., 2010; Koch et al., 2011) and that these enhancers are transcribed (Melgar et al., 2011; Wang et al., 2011). A role for these transcripts in enhancer function has been suggested (Orom and Shiekhattar, 2011), however their exact role remains uncertain. "
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