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Dynamic interplay between non-coding enhancer transcription and gene activity in development

Author

Listed:
  • Kota Hamamoto

    (The University of Tokyo
    The University of Tokyo)

  • Yusuke Umemura

    (The University of Tokyo
    The University of Tokyo)

  • Shiho Makino

    (The University of Tokyo)

  • Takashi Fukaya

    (The University of Tokyo
    The University of Tokyo)

Abstract

Non-coding transcription at the intergenic regulatory regions is a prevalent feature of metazoan genomes, but its biological function remains uncertain. Here, we devise a live-imaging system that permits simultaneous visualization of gene activity along with intergenic non-coding transcription at single-cell resolution in Drosophila. Quantitative image analysis reveals that elongation of RNA polymerase II across the internal core region of enhancers leads to suppression of transcriptional bursting from linked genes. Super-resolution imaging and genome-editing analysis further demonstrate that enhancer transcription antagonizes molecular crowding of transcription factors, thereby interrupting the formation of a transcription hub at the gene locus. We also show that a certain class of developmental enhancers are structurally optimized to co-activate gene transcription together with non-coding transcription effectively. We suggest that enhancer function is flexibly tunable through the modulation of hub formation via surrounding non-coding transcription during development.

Suggested Citation

  • Kota Hamamoto & Yusuke Umemura & Shiho Makino & Takashi Fukaya, 2023. "Dynamic interplay between non-coding enhancer transcription and gene activity in development," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36485-1
    DOI: 10.1038/s41467-023-36485-1
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    References listed on IDEAS

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    1. A. Marieke Oudelaar & Caroline L. Harrold & Lars L. P. Hanssen & Jelena M. Telenius & Douglas R. Higgs & Jim R. Hughes, 2019. "A revised model for promoter competition based on multi-way chromatin interactions at the α-globin locus," Nature Communications, Nature, vol. 10(1), pages 1-8, December.
    2. Lucas Farnung & Seychelle M. Vos & Patrick Cramer, 2018. "Structure of transcribing RNA polymerase II-nucleosome complex," Nature Communications, Nature, vol. 9(1), pages 1-6, December.
    3. Jessica Zuin & Gregory Roth & Yinxiu Zhan & Julie Cramard & Josef Redolfi & Ewa Piskadlo & Pia Mach & Mariya Kryzhanovska & Gergely Tihanyi & Hubertus Kohler & Mathias Eder & Christ Leemans & Bas Stee, 2022. "Nonlinear control of transcription through enhancer–promoter interactions," Nature, Nature, vol. 604(7906), pages 571-577, April.
    4. Sarah Djebali & Carrie A. Davis & Angelika Merkel & Alex Dobin & Timo Lassmann & Ali Mortazavi & Andrea Tanzer & Julien Lagarde & Wei Lin & Felix Schlesinger & Chenghai Xue & Georgi K. Marinov & Jaina, 2012. "Landscape of transcription in human cells," Nature, Nature, vol. 489(7414), pages 101-108, September.
    5. Robin Andersson & Claudia Gebhard & Irene Miguel-Escalada & Ilka Hoof & Jette Bornholdt & Mette Boyd & Yun Chen & Xiaobei Zhao & Christian Schmidl & Takahiro Suzuki & Evgenia Ntini & Erik Arner & Eivi, 2014. "An atlas of active enhancers across human cell types and tissues," Nature, Nature, vol. 507(7493), pages 455-461, March.
    6. Joseph A. Martens & Lisa Laprade & Fred Winston, 2004. "Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene," Nature, Nature, vol. 429(6991), pages 571-574, June.
    7. Evgeny Z. Kvon & Tomas Kazmar & Gerald Stampfel & J. Omar Yáñez-Cuna & Michaela Pagani & Katharina Schernhuber & Barry J. Dickson & Alexander Stark, 2014. "Genome-scale functional characterization of Drosophila developmental enhancers in vivo," Nature, Nature, vol. 512(7512), pages 91-95, August.
    8. Tae-Kyung Kim & Martin Hemberg & Jesse M. Gray & Allen M. Costa & Daniel M. Bear & Jing Wu & David A. Harmin & Mike Laptewicz & Kellie Barbara-Haley & Scott Kuersten & Eirene Markenscoff-Papadimitriou, 2010. "Widespread transcription at neuronal activity-regulated enhancers," Nature, Nature, vol. 465(7295), pages 182-187, May.
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