Fig. 7
From: Targeting G-quadruplex for rescuing impaired chondrogenesis in WRN-deficient stem cells
Illustration of G4 retainment in WS causing SHOX insufficiency and chondrogenic defect. Under normal chondrogenesis, WRN resolves SHOX promoter G4s to enhance SHOX expression. SHOX then promotes expression of chondrogenic genes to stimulate matrix synthesis. In WS, absence of helicase active WRN leads to aberrant G4s and thus inhibits SHOX expression. Gene rescue by Cas9/CRISPR acting on SHOX G4 sequences causes indel and prevents G4 formation. SHOX expression and chondrogenesis are restored in the absence of WRN