TWIST1

TWIST1, also known as Twist-related protein 1, is a gene that encodes a member of the basic helix-loop-helix (bHLH) family of transcription factors. The Twist1 protein binds DNA at E-box motifs (CANNTG) as a dimer with other bHLH proteins and regulates transcription of genes involved in development and cell behavior.

In development, Twist1 is essential for mesoderm formation and neural crest cell migration, contributing to craniofacial morphogenesis and limb development. It promotes epithelial-mesenchymal transition (EMT) in certain contexts, enabling cell movement by repressing epithelial markers such as E-cadherin and activating mesenchymal programs.

TWIST1 activity is regulated at transcriptional, post-transcriptional, and post-translational levels. Signaling pathways including TGF-β, Wnt, and Notch can upregulate TWIST1, while hypoxic conditions can induce its expression via HIF1α. The protein can be modified by phosphorylation and other modifications that affect its stability and activity.

Clinical relevance: Mutations in TWIST1 cause Saethre-Chotzen syndrome, an autosomal dominant craniosynostosis syndrome with limb anomalies. In cancer, TWIST1 is often overexpressed and correlates with enhanced metastatic potential, EMT, invasion, and resistance to therapy in various tumors, including breast and prostate cancer. These properties have made TWIST1 a focus of research as a potential therapeutic target.

Genomic and evolutionary notes: TWIST1 is conserved across vertebrates. The gene is distinct from TWIST2, a related family member with overlapping yet separate roles.