In silico identification of enhancers on the basis of a combination of transcription factor binding motif occurrences

Abstract

Enhancers interact with gene promoters and form chromatin looping structures that serve important functions in various biological processes, such as the regulation of gene transcription and cell differentiation. However, enhancers are difficult to identify because they generally do not have fixed positions or consensus sequence features, and biological experiments for enhancer identification are costly in terms of labor and expense. In this work, several models were built by using various sequence-based feature sets and their combinations for enhancer prediction. The selected features derived from a recursive feature elimination method showed that the model using a combination of 141 transcription factor binding motif occurrences from 1,422 transcription factor position weight matrices achieved a favorably high prediction accuracy superior to that of other reported methods. The models demonstrated good prediction accuracy for different enhancer datasets obtained from different cell lines/tissues. In addition, prediction accuracy was further improved by integration of chromatin state features. Our method is complementary to wet-lab experimental methods and provides an additional method to identify enhancers.

Epigenomic landscape of enhancer elements during Hydra head organizer formation

“…Enhancers can be categorized as active and poised enhancers. Active enhancers predominantly exhibit the H3K4me1 and H3K27ac modifications, whereas poised enhancers possess the H3K4me1 and H3K27me3 modifications [25]. Additionally, acetylation of H3 by p300 and related acetyltransferases on intergenic regions of the genome has been observed at enhancers [26,27].…”

DNA Methylation of Enhancer Elements in Myeloid Neoplasms: Think Outside the Promoters?

“…The advances in epigenomic profiling technologies such as ChIP-seq (chromatin immunoprecipitation followed by high-throughput sequencing) have been effectively used to correctly annotate them, associating putative enhancer regions with the presence of monomethylation of lysine 4 in histone 3 (H3K4me1) and acetylation of lysine 27 in histone 3 (H3K27ac) (Figure 1). These two modifications, often in combination with chromatin accessibility data provided by DNase-seq (sequencing of DNase I hypersensitive sites) or ATAC-seq (assay for transposable-accessible chromatin-sequencing), provide a robust readout of genome-wide location of active enhancers, and have been utilized for enhancer annotation in a myriad of studies [8,11,12,13,14]. These chromatin marks are not simply passive modifications, for instance, in primed or poised enhancers associated with H3K4me1 modification, addition of the methyl group to the histone tail can prevent DNA methylation, facilitate nucleosome repositioning, and promote the binding of the so called “pioneer” factors responsible for enhancer activation [15,16].…”

Gene expression changes during the evolution of the tetrapod limb

“…Modern in silico methods are not only able to locate conserved non-coding regions in genomes, but also capable of predicting transcription factor binding sites within them with high confidential rates (Oshchepkov and Levitsky 2011;Fang et al 2016;Vandel et al 2019). Thus, less conserved, taxon-or species-specific enhancers can be mapped, helping to understand the evolutionary background of different appendage morphologies.…”