: 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.

Alternatively spliced exon regulates context-dependent MEF2D higher-order assembly during myogenesis / Gönczi, Mónika; Teixeira, João M C; Barrera-Vilarmau, Susana; Mediani, Laura; Antoniani, Francesco; Nagy, Tamás Milán; Fehér, Krisztina; Ráduly, Zsolt; Ambrus, Viktor; Tőzsér, József; Barta, Endre; Kövér, Katalin E; Csernoch, László; Carra, Serena; Fuxreiter, Monika. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 14:1(2023), pp. 1-13. [10.1038/s41467-023-37017-7]

Alternatively spliced exon regulates context-dependent MEF2D higher-order assembly during myogenesis

Mediani, Laura;Antoniani, Francesco;Carra, Serena
;
2023

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.
2023
14
1
1
13
Alternatively spliced exon regulates context-dependent MEF2D higher-order assembly during myogenesis / Gönczi, Mónika; Teixeira, João M C; Barrera-Vilarmau, Susana; Mediani, Laura; Antoniani, Francesco; Nagy, Tamás Milán; Fehér, Krisztina; Ráduly, Zsolt; Ambrus, Viktor; Tőzsér, József; Barta, Endre; Kövér, Katalin E; Csernoch, László; Carra, Serena; Fuxreiter, Monika. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 14:1(2023), pp. 1-13. [10.1038/s41467-023-37017-7]
Gönczi, Mónika; Teixeira, João M C; Barrera-Vilarmau, Susana; Mediani, Laura; Antoniani, Francesco; Nagy, Tamás Milán; Fehér, Krisztina; Ráduly, Zsolt...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1299385
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