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journal article·2026-03Open access

Arginine Methylation Antagonizes TEAD3‐Mediated Repression to Promote Osteogenic Differentiation by Disrupting RUNX2‐Sequestrating Condensates

Lei Cao, Ruohui Han, Hui Xiong, Qian Li, Shaofei Tao, Xudong Wu, Dayong Liu

Advanced Science· Volume 13· Issue 16
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Source abstract

Abstract

ABSTRACT Osteogenic differentiation is essential for bone remodeling and repair. Protein arginine methyltransferases (PRMTs) regulate this process; however, their key substrates and mechanisms remain elusive. Here, we identify TEAD3, a TEA domain transcription factor mediating Hippo signaling output, as an arginine‐methylated regulator of periodontal ligament stem cells (PDLSCs) osteogenesis. Mechanistically, TEAD3 is methylated at arginine 55 (R55), a conserved residue within its DNA–binding TEA domain. Disruption of R55 methylation via R55K mutation enhances formation of TEAD3 homodimer condensates, which spatially constrain RUNX2 transcriptional activity without disrupting its Hippo signaling functions. Notably, the TEAD3‐R55K mutant exhibits heightened sensitivity to TEAi, a TEA domain‐ targeting inhibitory peptide. These findings unveil arginine methylation as a critical switch governing TEAD3‐mediated osteogenic commitment and highlight TEAD‐targeted strategies as promising therapeutics for bone regeneration.
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Research context

OpenAlex topics: Cancer-related gene regulation · Epigenetics and DNA Methylation · Hippo pathway signaling and YAP/TAZ

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

State Key Laboratory of Experimental Hematology The Province and Ministry Co‐sponsored Collaborative Innovation Center for Medical Epigenetics Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) Tianjin Key Laboratory of Medical Epigenetics Department of Endodontics Tianjin Medical University School and Hospital of Stomatology & Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration Tianjin Medical University Tianjin China

Department of Cell Biology Tianjin Medical University Tianjin China

Department of Pediatric Dentistry Hospital of Stomatology and Hebei Provincial Key Laboratory of Stomatology Hebei Medical University Shijiazhuang China

Department of Physiology and Pathophysiology Tianjin Medical University Tianjin China

International Science and Technology Cooperation Base of Spinal Cord Injury Department of Orthopedic Surgery Tianjin Medical University General Hospital Tianjin China

Shanghai Engineering Research Center of Tooth Restoration and Regeneration & Tongji Research Institute of Stomatology & Department of Endodontics Shanghai Tongji Stomatological Hospital and Dental School Tongji University Shanghai China

Funding

National Natural Science Foundation of China · Natural Science Foundation of Tianjin Municipality · Natural Science Foundation of Hebei Province

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