In this episode of the Epigenetics Podcast, we talked with Tae-Kyung Kim from POSTECH in South Korea about the discovery and characterisation of enhancer RNAs.

Dr. Kim describes joining Danny Reinberg’s lab as a graduate student, where he was trained in protein biochemistry and general transcription mechanisms. He recalls this period as a formative time, when research on transcription factors and RNA polymerase II was rapidly advancing and many findings were still novel.

Kim then moved into neurobiology through Michael Greenberg’s lab, where he first worked on a project related to L-type voltage-gated channels. He says his work shifted toward chromatin and gene regulation in neurons after learning that chromatin immunoprecipitation could be applied to neuronal systems and after the arrival of next-generation sequencing.

He explains that eRNAs were discovered in his lab through RNA-seq and ChIP-seq data from neuronal activity experiments, especially around the FOS locus. He later showed that eRNAs are transcribed from enhancers, are typically unstable, often lack splicing and polyadenylation, and have defined initiation sites, suggesting regulated transcription.

Kim says eRNAs can interact with transcription and epigenetic regulators, including factors involved in pause release and mediator complexes. He describes experiments showing that eRNA knockdown reduced ARC induction and that eRNA production depends on proper enhancer-promoter contact.

He concludes by describing newer work in his lab using spatial transcriptomics and eRNA-based reporter systems to map active neural populations, including studies related to cocaine-responsive circuits. He says his future work will focus on spatial technologies to better understand brain organization and function at molecular resolution.

References

Kim TK, Hemberg M, Gray JM, Costa AM, Bear DM, Wu J, Harmin DA, Laptewicz M, Barbara-Haley K, Kuersten S, Markenscoff-Papadimitriou E, Kuhl D, Bito H, Worley PF, Kreiman G, Greenberg ME. Widespread transcription at neuronal activity-regulated enhancers. Nature. 2010 May 13;465(7295):182-7. doi: 10.1038/nature09033. Epub 2010 Apr 14. PMID: 20393465; PMCID: PMC3020079.
Schaukowitch K, Joo JY, Liu X, Watts JK, Martinez C, Kim TK. Enhancer RNA facilitates NELF release from immediate early genes. Mol Cell. 2014 Oct 2;56(1):29-42. doi: 10.1016/j.molcel.2014.08.023. Epub 2014 Sep 25. PMID: 25263592; PMCID: PMC4186258.
Kim SK, Liu X, Park J, Um D, Kilaru G, Chiang CM, Kang M, Huber KM, Kang K, Kim TK. Functional coordination of BET family proteins underlies altered transcription associated with memory impairment in fragile X syndrome. Sci Adv. 2021 May 19;7(21):eabf7346. doi: 10.1126/sciadv.abf7346. PMID: 34138732; PMCID: PMC8133748.
Gorbovytska V, Kim SK, Kuybu F, Götze M, Um D, Kang K, Pittroff A, Brennecke T, Schneider LM, Leitner A, Kim TK, Kuhn CD. Enhancer RNAs stimulate Pol II pause release by harnessing multivalent interactions to NELF. Nat Commun. 2022 May 4;13(1):2429. doi: 10.1038/s41467-022-29934-w. PMID: 35508485; PMCID: PMC9068813.

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