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

Zhang, G.; Liu, H.; Li, L.; Zhang, Q.; Ott, C.

2025-12-11 biochemistry
10.64898/2025.12.10.693453 bioRxiv
Show abstract

Virus infection triggers the expression of IFN-x{beta}, 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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