The inner nuclear membrane protein LEMD3 organizes the 3D chromatin architecture to maintain vascular smooth muscle cell identity

Wenqiang Li, Yunxi Liao, Zhujiang Liu, Longjian Niu, Jiaqi Huang, Yiting Jia, Ran Xu, Sudun Guan, Zhenhui Liang, Yiran Li, Hao Wu, Shirong Zhu, Liao Tan, Fang Yu, Zhihua Wang, Luyang Sun, Dongyu Zhao (), Wei Kong () and Yi Fu ()
Additional contact information
Wenqiang Li: Peking University Health Science Center
Yunxi Liao: Peking University
Zhujiang Liu: Chinese Academy of Sciences
Longjian Niu: Southern University of Science and Technology
Jiaqi Huang: Peking University Health Science Center
Yiting Jia: Peking University
Ran Xu: Capital Medical University
Sudun Guan: Peking University Health Science Center
Zhenhui Liang: Peking University Health Science Center
Yiran Li: Peking University Health Science Center
Hao Wu: Peking University Health Science Center
Shirong Zhu: Peking University Health Science Center
Liao Tan: Central South University
Fang Yu: Peking University Health Science Center
Zhihua Wang: Fuwai Hospital Chinese Academy of Medical Sciences
Luyang Sun: Peking University Health Science Center
Dongyu Zhao: Peking University
Wei Kong: Peking University Health Science Center
Yi Fu: Peking University Health Science Center

Nature Communications, 2025, vol. 16, issue 1, 1-25

Abstract: Abstract Maintaining the contractile phenotype of vascular smooth muscle cells (VSMCs) is critical for vascular homeostasis. However, the role of the 3D chromatin architecture in regulating VSMC identity remains elusive. A genome-scale CRISPR screen identifies LEMD3 as a potential regulator to maintain VSMC identity. Lemd3 deficiency in VSMCs results in the loss of the contractile phenotype and exacerbates intimal hyperplasia in mice. Protein interactome analysis reveals that LEMD3 interacts with CBX3, a principal reader of H3K9me2/3, subsequently anchoring heterochromatin at the nuclear periphery. Employing the DNA polymer model based on Hi-C data, whole-chromosome simulations demonstrate that Lemd3 depletion disturbs the chromatin structure. Multi-omics analysis further reveals that Lemd3 depletion alters the genome conformation as the increase of inter-TAD (topologically associated domain) interactions at the boundaries of A and B compartments, which correlates with decreased chromatin accessibility and repressed expression of VSMC contractile genes. This study reveals that LEMD3 organizes the 3D chromatin architecture by anchoring heterochromatin at the nuclear periphery to maintain the VSMC contractile identity.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-63876-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63876-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-63876-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().