Work

Fluctuating Chromatin Facilitates Enhancer–Promoter Communication by Regulating Transcriptional Clustering Dynamics

Year: 2024

Type: article

Abstract: Enhancers regulate gene expression by forming contacts with distant promoters. Phase-separated condensates or clusters formed by transcription factors (TFs) and cofactors are thought to facilitate these enhancer-promoter (E-P) interactions. Using polymer physics, we developed distinct coarse-grained chromatin models that produce similar ensemble-averaged Hi-C maps but with "stable" and "dynamic" characteristics. Our findings, consistent with recent experiments, reveal a multistep E-P communication process. The dynamic model facilitates E-P proximity by enhancing TF clustering and subsequently promotes direct E-P interactions by destabilizing the TF clusters through chain flexibility. Our study promotes physical understanding of the molecular mechanisms governing E-P communication in transcriptional regulation.

Source: The Journal of Physical Chemistry Letters

DOI: 10.1021/acs.jpclett.4c02453

Authors: Tao Zhu, Chunhe Li, Xiakun Chu

Institutions: Fudan University, Hong Kong University of Science and Technology, The Hong Kong University of Science and Technology (Guangzhou)

Language: English

Topic: Genomics and Chromatin Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green