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Noncoding function of super enhancer derived Cpox pre-mRNA in modulating neighbouring gene expression and chromatin
1Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
RNA Biology
|March 7, 2025
Summary
Super enhancers can regulate gene expression. This study reveals that the pre-mRNA from the Cpox gene within a super enhancer has a non-coding function, impacting gene regulation and enhancer activity.
Area of Science:
- Molecular Biology
- Genetics
- Epigenetics
Background:
- Super enhancers are crucial for gene expression regulation.
- The role of protein-coding genes and their transcripts overlapping with super enhancers is not fully understood.
Purpose of the Study:
- To investigate the function of pre-mRNA transcribed from a super enhancer-overlapping gene.
- To explore the regulatory mechanisms involving pre-mRNA, enhancer activity, and 3D genome organization.
Main Methods:
- Utilized an erythroid-specific super enhancer model overlapping the Cpox gene.
- Performed Cpox pre-mRNA depletion experiments.
- Analyzed H3K27me3 accumulation, p300 release, and enhancer activity.
- Investigated inter-gene interactions and TAD structures.
Main Results:
- Cpox pre-mRNA exhibits non-coding functions, regulating neighboring genes, eRNA expression, and TAD interactions.
- Cpox pre-mRNA depletion causes H3K27me3 accumulation and p300 release, activating an intra-TAD enhancer.
- A novel head-to-tail interaction between Cpox and Dcbld2, mediated by a repressive loop involving p300 and PRC2/H3K27me3, was identified.
Conclusions:
- Pre-mRNA transcribed within super enhancers plays a regulatory role in gene expression.
- Discovered a novel mechanism of head-to-tail inter-gene interaction influencing gene regulation and potential oncogene activation.
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