NIH Research Festival
Super enhancers are important regulators of gene expression that often overlap with protein-coding genes. However, it is unclear whether the overlapping protein-coding genes and the mRNA derived from them contribute to enhancer activity. Using an erythroid-specific super enhancer that overlaps the CPOX gene as a model, we found that CPOX mRNA has a non-coding function in regulating neighboring protein-coding genes, eRNA expression and TAD interactions. Depletion of CPOX mRNA leads to accumulation of H3K27me3 and release of p300 from the CPOX locus, activating intra-TAD enhancer and gene expression. Additionally, we identified a transcription start site-transcription termination site (TSS-TTS) interaction between the TAD boundary genes CPOX and DCBLD2 that is facilitated by a novel type of repressive loop anchored by p300 and PRC2/H3K27me3. Our results uncover a regulatory role for mRNA transcribed within a super enhancer context and provide insights into head-to-tail inter-gene interaction in the regulation of gene expression.
Scientific Focus Area: Chromosome Biology
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