Fig. 2: RUNX2 QA repeat length determines protein transactivation.

Schematic of RUNX2 QA repeat mode of action. a QA repeat lengths form a “goldilocks” range that determines function. Short repeats are less functional than medium length repeats, while expanded repeats form protein aggregates, reducing function. b Hypothetical mechanism of action where increasing repeat length promotes interactions with transcriptional co-factors, increasing gene expression (arrows) before hitting a critical threshold inhibiting activity. c QA repeat-driven changes to protein transactivation and downstream gene expression is suggested to fine-tune craniofacial length in several groups of mammals and can cause disease when in excess. OSE osteocalcin-specific element that occurs in osteogenic gene promotors.