Transcriptional regulation during mesenchymal cell differentiation: The role of coactivators

We have begun to understand the molecular mechanisms involved in the differentiation of pluripotent mesenchymal stem cells through the identification and characterization of the sequence-specific DNA-binding transcriptional activators that control differentiation along specific lineages. However, recent progress in the study of the mechanisms of gene transcription has identified an additional class of proteins essential for activated gene transcription, namely, the coactivators (sometimes also referred to as adaptors, mediators, or integrator molecules). This review focuses on the identified coactivators that could play a regulatory role in the differentiation of mesenchymal precursors along the myogenic and osteoblastic programs. Interestingly, one such coactivator specifically expressed in bone cells during development, alpha NAC (Nascent-polypeptide-associated complex And Coactivator alpha), is converted into a DNA-binding activator by differential splicing in differentiated myotubes. This suggests that NAC isoforms may be involved in multiple steps along the lineage-making decisions facing pluripotent mesenchymal precursors.