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Differential regulation of alternative promoters emerges from unified kinetics of enhancer-promoter interaction

Author

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  • Jingyao Wang

    (Shanghai Jiao Tong University
    Shanghai Jiao Tong University)

  • Shihe Zhang

    (Shanghai Jiao Tong University
    Shanghai Jiao Tong University)

  • Hongfang Lu

    (Shanghai Jiao Tong University
    Shanghai Jiao Tong University)

  • Heng Xu

    (Shanghai Jiao Tong University
    Shanghai Jiao Tong University)

Abstract

Many eukaryotic genes contain alternative promoters with distinct expression patterns. How these promoters are differentially regulated remains elusive. Here, we apply single-molecule imaging to quantify the transcriptional regulation of two alternative promoters (P1 and P2) of the Bicoid (Bcd) target gene hunchback in syncytial blastoderm Drosophila embryos. Contrary to the previous notion that Bcd only activates P2, we find that Bcd activates both promoters via the same two enhancers. P1 activation is less frequent and requires binding of more Bcd molecules than P2 activation. Using a theoretical model to relate promoter activity to enhancer states, we show that the two promoters follow common transcription kinetics driven by sequential Bcd binding at the two enhancers. Bcd binding at either enhancer primarily activates P2, while P1 activation relies more on Bcd binding at both enhancers. These results provide a quantitative framework for understanding the kinetic mechanisms of complex eukaryotic gene regulation.

Suggested Citation

  • Jingyao Wang & Shihe Zhang & Hongfang Lu & Heng Xu, 2022. "Differential regulation of alternative promoters emerges from unified kinetics of enhancer-promoter interaction," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30315-6
    DOI: 10.1038/s41467-022-30315-6
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    References listed on IDEAS

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