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Noncoding function of super enhancer derived mRNA in modulating neighboring gene expression and TAD interaction
1Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Biorxiv : the Preprint Server for Biology
|December 18, 2023
Summary
Messenger RNA from the Cpox gene, within a super enhancer, regulates gene expression and chromatin interactions. Cpox mRNA depletion alters epigenetic marks and gene activation, revealing a novel non-coding function.
Area of Science:
- Genomics
- Molecular Biology
- Epigenetics
Background:
- Super enhancers significantly influence gene expression, often overlapping protein-coding genes.
- The functional role of overlapping protein-coding genes and their derived mRNA in enhancer activity remains largely unexplored.
Approach:
- Utilized an erythroid-specific super enhancer overlapping the Cpox gene as a model system.
- Investigated the non-coding functions of Cpox mRNA in regulating gene expression, eRNA, and TAD interactions.
- Examined the effects of Cpox mRNA depletion on epigenetic modifications (H3K27me3, p300 binding) and enhancer activity.
Key Points:
- Cpox mRNA exhibits non-coding regulatory functions on neighboring genes, eRNA expression, and Topologically Associating Domain (TAD) interactions.
- Depletion of Cpox mRNA results in H3K27me3 accumulation and p300 release, activating an intra-TAD enhancer.
- A novel repressive loop involving p300 and PRC2/H3K27me3 mediates head-to-tail interactions between TAD boundary genes Cpox and Dcbld2.
Conclusions:
- mRNA transcribed within super enhancers plays a regulatory role in gene expression.
- Uncovered a novel mechanism of head-to-tail inter-gene interaction influencing gene expression and oncogene activation.
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