Enhancer/Enhanceosome/Super-enhancer and the promoter-proximate RNA Polymerase II (Pol II) pausing are coupled

2025 · doi:10.64898/2025.12.10.693453
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Abstract

Virus infection triggers the expression of IFN-xβ, which requires at least four groups of transcription factors and p300/CBP to form an enhanceosome. The promoter-proximal Pol II pausing regulation in metazoans includes the recruitment of CDK9 by JMJD6 and BRD4, the generation of a unique phosphorylation pattern of CTD of Pol II, the recruitment of JMJD5, and the cleavage of arginine methylated histone tails on the +1 nucleosome. We find that both BRD4 and p300/CBP control the activity of CDK9. It is likely that the BRD4 docking site on nucleosomes is generated by p300/CBP. We conclude that enhancer/enhanceosome/super-enhancer and Pol II pausing regulation are coupled and could be the unique universal mechanism that differentiates animals from unicellular organisms.
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Abstract Virus infection triggers the expression of IFN-xβ, which requires at least four groups of transcription factors and p300/CBP to form an enhanceosome. The promoter-proximal Pol II pausing regulation in metazoans includes the recruitment of CDK9 by JMJD6 and BRD4, the generation of a unique phosphorylation pattern of CTD of Pol II, the recruitment of JMJD5, and the cleavage of arginine methylated histone tails on the +1 nucleosome. We find that both BRD4 and p300/CBP control the activity of CDK9. It is likely that the BRD4 docking site on nucleosomes is generated by p300/CBP. We conclude that enhancer/enhanceosome/super-enhancer and Pol II pausing regulation are coupled and could be the unique universal mechanism that differentiates animals from unicellular organisms. Competing Interest Statement GZ holds equity in NB Life Laboratory, LLC, Colorado, USA Footnotes Conflicts of interest: GZ holds equity in NB Life Laboratory LLC

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License: Public-Domain