Abstract
Transcriptional enhancers play critical roles in regulation of gene expression, but their identification in the eukaryotic genome has been challenging. Recently, it was shown that enhancers in the mammalian genome are associated with characteristic histone modification patterns, which have been increasingly exploited for enhancer identification. However, only a limited number of cell types or chromatin marks have previously been investigated for this purpose, leaving the question unanswered whether there exists an optimal set of histone modifications for enhancer prediction in different cell types. Here, we address this issue by exploring genome-wide profiles of 24 histone modifications in two distinct human cell types, embryonic stem cells and lung fibroblasts. We developed a Random-Forest based algorithm, RFECS (Random Forest based Enhancer identification from Chromatin States) to integrate histone modification profiles for identification of enhancers, and used it to identify enhancers in a number of cell-types. We show that RFECS not only leads to more accurate and precise prediction of enhancers than previous methods, but also helps identify the most informative and robust set of three chromatin marks for enhancer prediction.
Highlights
Enhancers are distal regulatory elements with key roles in the regulation of gene expression
Determining the genome-wide binding sites of transcriptional coactivator p300 is one way of finding enhancers but it can only identify a subset of enhancers
A few years ago, it was observed that the binding sites of p300 are marked by distinctive, post-translational histone modifications
Summary
Enhancers are distal regulatory elements with key roles in the regulation of gene expression. The first is mapping the binding sites of specific transcription factors by ChIP-seq [14] Because this approach requires the knowledge of a subset of transcription factors (TFs) that are expressed and occupy all active enhancer regions in the cell-type of interest, identification of all enhancers using this approach is not a trivial task. A fourth approach interrogates covalent modifications of histones [5,23,24,25,26] as it was observed that certain histone modifications form a consistent signature of enhancers. It is on this approach that the present work is focused
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