ArticleNature communications2023
Alternatively spliced exon regulates context-dependent MEF2D higher-order assembly during myogenesis.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Biomolecular condensates as dynamic regulators of musculoskeletal homeostasis, disease, and therapeutic challenges.Bone research · 2026Review
- The Diverse Roles of the MEF2 Transcription Factor Family in Tumor Progression and Emerging Therapeutic Opportunities.Biomedicines · 2026Review
- FuzDrop: sequence-based prediction of the propensity of proteins for liquid-liquid phase separation and aggregation.Nature protocols · 2026Review
- Alternative splicing dynamics during human cardiac development in vivo and in vitro.Stem cell reports · 2026Article
- The muscle specific MEF2Dα2 isoform promotes muscle ketolysis and running capacity in mice.EMBO reports · 2025Article
- How proteins sense their cellular environment.Nature reviews. Molecular cell biology · 2025Article
- Toward universal models for collective interactions in biomolecular condensates.Biophysics reviews · 2025Article
- The Spatial-Temporal Alternative Splicing Profile Reveals the Functional Diversity of FXR1 Isoforms in Myogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Fuzzy protein-DNA interactions and beyond: A common theme in transcription?Current opinion in structural biology · 2024Review
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During muscle cell differentiation, the alternatively spliced, acidic β-domain potentiates transcription of Myocyte-specific Enhancer Factor 2 (Mef2D). Sequence analysis by the FuzDrop method indicates that the β-domain can serve as an interaction element for Mef2D higher-order assembly. In accord, we observed Mef2D mobile nuclear condensates in C2C12 cells, similar to those formed through liquid-liquid phase separation. In addition, we found Mef2D solid-like aggregates in the cytosol, the presence of which correlated with higher transcriptional activity. In parallel, we observed a progress in the early phase of myotube development, and higher MyoD and desmin expression. In accord with our predictions, the formation of aggregates was promoted by rigid β-domain variants, as well as by a disordered β-domain variant, capable of switching between liquid-like and solid-like higher-order states. Along these lines, NMR and molecular dynamics simulations corroborated that the β-domain can sample both ordered and disordered interactions leading to compact and extended conformations. These results suggest that β-domain fine-tunes Mef2D higher-order assembly to the cellular context, which provides a platform for myogenic regulatory factors and the transcriptional apparatus during the developmental process.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.