Abstract
BackgroundTranscriptional enhancers are generally known to regulate gene transcription from afar. Their activation involves a series of changes in chromatin marks and recruitment of protein factors. These enhancers may also occur inside genes, but how many may be active in human cells and their effects on the regulation of the host gene remains unclear.ResultsWe describe a novel semi-supervised method based on the relative enrichment of chromatin signals between 2 conditions to predict active enhancers. We applied this method to the tumoral K562 and the normal GM12878 cell lines to predict enhancers that are differentially active in one cell type. These predictions show enhancer-like properties according to positional distribution, correlation with gene expression and production of enhancer RNAs. Using this model, we predict 10,365 and 9777 intragenic active enhancers in K562 and GM12878, respectively, and relate the differential activation of these enhancers to expression and splicing differences of the host genes.ConclusionsWe propose that the activation or silencing of intragenic transcriptional enhancers modulate the regulation of the host gene by means of a local change of the chromatin and the recruitment of enhancer-related factors that may interact with the RNA directly or through the interaction with RNA binding proteins. Predicted enhancers are available at http://regulatorygenomics.upf.edu/Projects/enhancers.html.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1704-0) contains supplementary material, which is available to authorized users.
Highlights
Transcriptional enhancers are generally known to regulate gene transcription from afar
We propose that the activation or silencing of intragenic transcriptional enhancers can modulate the regulation of the host gene through a local change of the chromatin
Using windows along the entire genome (Additional file 1: Figures S1 and S2), we considered the relative enrichment of a number of histone marks and protein factors (Methods)
Summary
Transcriptional enhancers are generally known to regulate gene transcription from afar. Intragenic enhancers can regulate the expression of the host gene [14] or of a nearby gene [15], and have been proposed to act as alternative promoters [16] These results raise the question of how many intragenic enhancers may be active in a cell and whether upon their activation or silencing they may affect the processing of the host gene, possibly by means of local changes of the chromatin state. In this direction, there is evidence that some enhancers upstream of a reporter gene can affect splicing in vitro [17], and that intragenic enhancers bound by Argonaute-1 (AGO1) protein can González-Vallinas et al BMC Genomics (2015) 16:523 affect the constitutive and alternative splicing of the host gene [18]. We propose that the activation or silencing of intragenic transcriptional enhancers can modulate the regulation of the host gene through a local change of the chromatin
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