Muscle differentiation is antagonized by SOX15, a new member of the SOX protein family

SOX proteins belong to a multigenic family characterized by a unique DNA bi nding domain, known as the high mobility group box, that is related to that of the testis determining gene SRY, cDNA sequences for more than 30 SOX ge nes have been identified, and some are known to have diverse roles in verte brate differentiation and development. Here, we report the isolation and ch aracterization of mouse Sox15 that was uncovered during a screen for high m obility group box containing transcription factors that are expressed at di fferent levels during skeletal muscle differentiation. Sox15 cDNAs were fou nd at a much higher frequency in myoblasts prior to their differentiation i nto myotubes, Electrophoretic mobility shift assays indicated that recombin ant SOX15 protein was capable of binding to a consensus DNA binding site fo r SOX proteins. When overexpressed in C2C12 myoblasts, wild type SOX15, but not a C-terminal truncated form or the related protein SOX11, specifically inhibited activation of muscle-specific genes and expression of the basic helix-loop-helix myogenic factors myogenin and MyoD, resulting in a failure of the cells to differentiate into myotubes, These results suggest a speci fic and repressive role for SOX15, requiring the C-terminal domain, during myogenesis.