Quantitative Proteomic Identification of MAZ as a Transcriptional Regulator of Muscle-Specific Genes in Skeletal and Cardiac Myocytes

摘要: We identified a conserved sequence within the Muscle creatine kinase (MCK) promoter that is critical for high-level activity in skeletal and cardiac myocytes (MCK Promoter Element X [MPEX]). After selectively enriching MPEX-binding factor(s) (MPEX-BFs), ICAT-based quantitative proteomics was used to identify MPEX-BF candidates, one of which MAZ (Myc-associated zinc finger protein). transactivates MCK binds MPEX site vitro, chromatin immunoprecipitation analysis demonstrates enrichment at endogenous other muscle gene promoters (Skeletal α-actin, Desmin, α-Myosin heavy chain) myocytes. Consistent with its role transcription, transcripts DNA-binding are upregulated during myocyte differentiation. Furthermore, shown bind numerous sequences (e.g., CTCCTCCC CTCCACCC) diverge from GA box binding motif. Alternate motifs were many promoters, including Myogenin MEF2C, motif be Six4 both Interestingly, occupies able transactivate but not Taken together, these findings consistent previously unrecognized regulation.