Work

Cohesin prevents cross-domain gene coactivation

Year: 2024

Type: article

Abstract: The contrast between the disruption of genome topology after cohesin loss and the lack of downstream gene expression changes instigates intense debates regarding the structure–function relationship between genome and gene regulation. Here, by analyzing transcriptome and chromatin accessibility at the single-cell level, we discover that, instead of dictating population-wide gene expression levels, cohesin supplies a general function to neutralize stochastic coexpression tendencies of cis -linked genes in single cells. Notably, cohesin loss induces widespread gene coactivation and chromatin co-opening tens of million bases apart in cis . Spatial genome and protein imaging reveals that cohesin prevents gene co-bursting along the chromosome and blocks spatial mixing of transcriptional hubs. Single-molecule imaging shows that cohesin confines the exploration of diverse enhancer and core promoter binding transcriptional regulators. Together, these results support that cohesin arranges nuclear topology to control gene coexpression in single cells.

Source: Nature Genetics

DOI: 10.1038/s41588-024-01852-1

Authors: Peng Dong, Shu Zhang, Valentina Gandin, Liangqi Xie, Lihua Wang, Andrew L. Lemire, Wenhong Li, Hideo Otsuna, Takashi Kawase, Arthur D. Lander, Howard Y. Chang, Zhe J. Liu

Institutions: Howard Hughes Medical Institute, Janelia Research Campus, Chinese Academy of Sciences, Shenzhen Institutes of Advanced Technology, Stanford University, Cleveland Clinic, Cleveland Clinic Research, University of California, Irvine

Language: English

Topic: Genomics and Chromatin Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $12,290

Funders: Howard Hughes Medical Institute, U.S. Department of Health and Human Services, Ministry of Science and Technology of the People's Republic of China, National Institutes of Health, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Dental and Craniofacial Research

Awards: Investigating the multifactorial origins of congenital heart disease, Center for Personal Dynamic Regulomes, G2911980784, Fluorender: An Imaging Tool for Visualization and Analysis of Confocal Data as Ap, G3956374251, G4175164298, G500699600, G5184401518, G638434084, LncRNA mechanisms in cancer, Complexity, Cooperation and Community in Cancer, G9000175280, G9000187983, G9000326434, G9000337004, The role of continuous phenotypic variation in structural defects of the face

OpenAlex ID: W4400956165

FWCI: 2.829

Cites: 89

Cited by: 21

Related to: 10