Journal article

The methyltransferase SMYD3 mediates the recruitment of transcriptional cofactors at the myostatin and c-Met genes and regulates skeletal muscle atrophy

Valentina Proserpio, Raffaella Fittipaldi, James G Ryall, Vittorio Sartorelli, Giuseppina Caretti

GENES & DEVELOPMENT | COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT | Published : 2013

Abstract

Elucidating the epigenetic mechanisms underlying muscle mass determination and skeletal muscle wasting holds the potential of identifying molecular pathways that constitute possible drug targets. Here, we report that the methyltransferase SMYD3 modulates myostatin and c-Met transcription in primary skeletal muscle cells and C2C12 myogenic cells. SMYD3 targets the myostatin and c-Met genes and participates in the recruitment of the bromodomain protein BRD4 to their regulatory regions through protein-protein interaction. By recruiting BRD4, SMYD3 favors chromatin engagement of the pause-release factor p-TEFb (positive transcription elongation factor) and elongation of Ser2-phosphorylated RNA p..

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University of Melbourne Researchers

Grants

Awarded by Associazione Italiana per la Ricerca sul Cancro (AIRC)


Awarded by NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES


Funding Acknowledgements

We thank A. Derfoul for help with satellite cell isolation protocol. The support of Associazione Italiana per la Ricerca sul Cancro (AIRC) MFAG 5386 and Marie Curie PIRGES-224833 to G.C. is kindly acknowledged. This work was supported in part by the Intramural Research Program of the National Institute of Arthritis, Musculoskeletal, and Skin Diseases of the National Institutes of Health.