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Our data show that, following TGF\u03b2 induction, SETDB1 accumulates in the nuclei of healthy myotubes while being already present in the nuclei of DMD myotubes where TGF\u03b2 signaling is constitutively activated. Transcriptomics revealed that depletion of SETDB1 in DMD myotubes leads to down-regulation of TGF\u03b2 target genes coding for secreted factors involved in extracellular matrix remodeling and inflammation. Consequently, SETDB1 silencing in DMD myotubes abrogates the deleterious effect of their secretome on myoblast differentiation by impairing myoblast pro-fibrotic response. Our findings indicate that SETDB1 potentiates the TGF\u03b2\u2013driven fibrotic response in DMD muscles, providing an additional axis for therapeutic intervention.<\/jats:p>","DOI":"10.1126\/sciadv.adj8042","type":"journal-article","created":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T13:58:46Z","timestamp":1714571926000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":6,"title":["SETDB1 modulates the TGF\u03b2 response in Duchenne muscular dystrophy myotubes"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1798-0686","authenticated-orcid":true,"given":"Alice","family":"Granados","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, Epigenetics and Cell Fate, UMR7216, F-75013 Paris, 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