A semi-supervised approach uncovers thousands of intragenic enhancers differentially activated in human cells

BioRxiv : the Preprint Server for Biology
Juan González-VallinasEduardo Eyras

Abstract

Background Transcriptional 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. Results We 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 9,777 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. Conclusions We 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 enhance...Continue Reading

Related Concepts

Chromatin
Gene Expression
Genes
RNA
RNA Splicing
Transcription, Genetic
RNA-Binding Proteins
Cell Line, Tumor
Research Methodology
Neoplastic Cell

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