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Transcription-coupled changes in higher-order genomic structure and transcription hub viscosity prolong enhancer-promoter connectivity

Ohishi, H.; Shinkai, S.; Owada, H.; Fujii, T.; Hosoda, K.; Onami, S.; Yamamoto, T.; Ohkawa, Y.; Ochiai, H.

2023-11-27 molecular biology
10.1101/2023.11.27.568629 bioRxiv
Show abstract

The orchestration of our genes heavily relies on a coordinated communication between enhancers and promoters, yet how this dynamic interplay remains elusive while transcription is active. Here, we investigated enhancer-promoter (E-P) interactions and relative to transcriptional bursting in mouse embryonic stem cells using sequential DNA/RNA/immunofluorescence (IF)-FISH analyses and computational simulations. Our data reveal that the active state of specific genes is characterized by higher-order genomic structures and local condensates of transcriptional regulatory factors, leading to an elevation in local viscosity that highly stabilizes the duration of E-P interactions. Our study underscores the pivotal role of viscosity in transcriptional dynamics and paves the way for a more nuanced understanding of gene-specific regulatory mechanisms.

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