An unexpected role of TAFs and TRFs in skeletal muscle differentiation: switching core promoter complexes

Sequence-specific enhancer-binding transcription factors and chromatin-modifying proteins are well recognized for their potential contributions to cell-type-specific gene regulation. In contrast, the role of core promoter recognition factors, such as TFIID in modulating gene- and cell-type-specific programs of transcription has been less understood. In general, the so-called basal factors have largely been relegated to a supporting role as invariant components of the preinitiation complex. To dissect the potential contributions of TFIID to cell-type-specific transcription, we have studied the developmental process of skeletal myogenesis. Terminal differentiation during myogenesis involves an intricate reprogramming of transcription that is thought to be directed by cell-type-specific transcription regulatory factors. Here, we summarize our findings that the canonical TFIID complex must first be dismantled as a requisite step during the differentiation of myoblasts into myotubes and subsequently substituted by a novel core transcription complex composed of TAF3 and TRF3. Although this remarkable mechanism of completely switching core promoter recognition complexes to drive terminal differentiation has not been previously documented, it may eventually prove to be the rule rather than the exception as we learn more about cell-type-specific gene regulation.