Mechanisms of transcription control by distal enhancers from high-resolution single-gene imaging

Cheng, L.; De, C.; Li, J.; Pertsinidis, A.

doi:10.1101/2023.03.19.533190

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bioRxiv · 10.1101/2023.03.19.533190

Mechanisms of transcription control by distal enhancers from high-resolution single-gene imaging

Cheng, L.·De, C.·Li, J.·Pertsinidis, A.

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Abstract

How distal enhancers physically control promoters over large genomic distances, to enable cell-type specific gene expression, remains obscure. Using single-gene super-resolution imaging and acute targeted perturbations, we define physical parameters of enhancer-promoter communication and elucidate processes that underlie target gene activation. Productive enhancer-promoter encounters happen at 3D distances {delta}200 nm - a spatial scale corresponding to unexpected enhancer-associated clusters of general transcription factor (GTF) components of the Pol II machinery. Distal activation is achieved by increasing transcriptional bursting frequency, a process facilitated by embedding a promoter into such GTF clusters and by accelerating an underlying multi-step cascade comprising early phases in the Pol II transcription cycle. These findings help clarify molecular/biochemical signals involved in long-range activation and their means of transmission from enhancer to promoter.

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Cheng, L., De, C., Li, J., Pertsinidis, A.. 2023-03-21. Mechanisms of transcription control by distal enhancers from high-resolution single-gene imaging. https://doi.org/10.1101/2023.03.19.533190

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