MADS-Box (DNA-binding domain)

**What it means:** The MADS-box is a ~58 amino acid DNA-binding domain — a specific region of the MEF2C protein that acts like a **grip** or **claw** that grabs onto specific DNA sequences. It's the part of the protein that literally holds onto the DNA so MEF2C can do its job as a transcription factor. **Analogy:** If MEF2C is a key that unlocks genes, the MADS-box is the teeth of the key — the part that actually fits into the lock. Mutations in this region tend to be more severe because they prevent MEF2C from binding DNA at all. This is part of why different mutation types (MADS-box vs. outside it) can have different phenotypic effects.