Transcription Factor Acetylation and Cell Fate Control: A Molecular Switch in Hematopoiesis and Myogenesis

Transcription factor acetylation is a critical yet often overlooked regulator of cell fate. Although traditionally studied in the context of histone modifications, many acetyltransferases and deacetylases also modify transcription factors directly, thereby controlling lineage-specific transcriptional programs. At the molecular level, acetylation fine-tunes transcription factor activity by modulating DNA binding, protein stability, cofactor interactions, and nucleo-cytoplasmic trafficking. These molecular effects frequently intersect with other post-translational modifications, establishing acetylation as a versatile molecular switch of transcriptional output. These molecular effects scale into cellular outcomes that determine identity and plasticity. In pluripotent stem cells, defined acetylation events on core regulators stabilize the pluripotency network and prime lineage-specific enhancers. In hematopoiesis, transcription factor acetylation modulates transitions from stem and progenitor states to committed lineages, while in myogenesis, it governs progenitor differentiation and regenerative capacity. Importantly, differential acetylation of distinct lysine residues can yield context-dependent outcomes, underscoring the precision and adaptability of this modification in controlling cell identity. Recognizing transcription factor acetylation as a central axis of epigenetic regulation reframes our understanding of lineage specification and cellular plasticity. Beyond developmental biology, it provides a mechanistic rationale for therapeutic strategies that target acetylation dynamics, not only altering chromatin states but also reprogramming transcription factor function. This review synthesizes current knowledge of transcription factor acetylation in hematopoietic and myogenic contexts, highlighting its significance as a bridge between molecular mechanisms and cellular identity, and as a promising target in disease intervention.