Enhancer occlusion transcripts regulate the activity of human enhancer domains via transcriptional interference: a computational perspective

Nucleic Acids Research
Amit PandeCarsten A Raabe

Abstract

Analysis of ENCODE long RNA-Seq and ChIP-seq (Chromatin Immunoprecipitation Sequencing) datasets for HepG2 and HeLa cell lines uncovered 1647 and 1958 transcripts that interfere with transcription factor binding to human enhancer domains. TFBSs (Transcription Factor Binding Sites) intersected by these 'Enhancer Occlusion Transcripts' (EOTrs) displayed significantly lower relative transcription factor (TF) binding affinities compared to TFBSs for the same TF devoid of EOTrs. Expression of most EOTrs was regulated in a cell line specific manner; analysis for the same TFBSs across cell lines, i.e. in the absence or presence of EOTrs, yielded consistently higher relative TF/DNA-binding affinities for TFBSs devoid of EOTrs. Lower activities of EOTr-associated enhancer domains coincided with reduced occupancy levels for histone tail modifications H3K27ac and H3K9ac. Similarly, the analysis of EOTrs with allele-specific expression identified lower activities for alleles associated with EOTrs. ChIA-PET (Chromatin Interaction Analysis by Paired-End Tag Sequencing) and 5C (Carbon Copy Chromosome Conformation Capture) uncovered that enhancer domains associated with EOTrs preferentially interacted with poised gene promoters. Analysis of EO...Continue Reading

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Datasets Mentioned

BETA
GSE34448
GSE29611
GSE2735
GSE62046
GSM970288
GSM970211

Methods Mentioned

BETA
RNA-seq
ChIP-Seq
acetylation

Software Mentioned

R
Circos
Bowtie
WebLogo
Mango
GATK
PscanChIP
DiffBind
CEAS
CEAS cis element annotation system

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