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Updated: Dec 27, 2025
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Dissection of Enhancer Function Using Multiplex CRISPR-based Enhancer Interference in Cell Lines
Published on: June 2, 2018
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Enhancer occlusion transcripts regulate the activity of human enhancer domains via transcriptional interference: a
Amit Pande1,2,3, Wojciech Makalowski3, Jürgen Brosius1,2,4
1Institute of Experimental Pathology, Centre for Molecular Biology of Inflammation (ZMBE), University of Münster, Von-Esmarch-Strasse 56, D-48149 Münster, Germany.
Nucleic Acids Research
|March 6, 2020
Summary
Long non-coding RNAs, termed Enhancer Occlusion Transcripts (EOTrs), interfere with transcription factor binding at human enhancer DNA. This interference impacts gene regulation and enhancer activity, revealing a novel mechanism of transcriptional control.
Area of Science:
- Genomics
- Molecular Biology
- Epigenetics
Background:
- Enhancers are crucial regulatory DNA elements controlling gene expression.
- Transcription factors (TFs) bind enhancers to modulate gene activity.
- The role of long non-coding RNAs in regulating TF binding at enhancers is not fully understood.
Purpose of the Study:
- To identify and characterize transcripts that interfere with TF binding to human enhancer domains.
- To investigate the impact of these transcripts on enhancer activity and gene regulation.
- To elucidate the mechanism by which these transcripts regulate enhancers.
Main Methods:
- Analysis of ENCODE long RNA-Seq and ChIP-seq datasets.
- Computational analysis of Transcription Factor Binding Sites (TFBSs).
- Integration of ChIA-PET, 5C, and GRO-seq data.
Main Results:
- Identified 1647-1958 'Enhancer Occlusion Transcripts' (EOTrs) interfering with TF binding.
- EOTrs significantly reduced TF binding affinity and enhancer activity (H3K27ac, H3K9ac).
- EOTrs correlate with RNA polymerase pausing and preferential interaction with poised gene promoters.
Conclusions:
- EOTr expression regulates human enhancer activity through transcriptional interference.
- This mechanism impacts TF binding, enhancer-TF interactions, and gene expression.
- EOTrs represent a novel layer of gene regulation at the enhancer level.
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