Targeting G-quadruplex for rescuing impaired chondrogenesis in WRN-deficient stem cells.

ABSTRACT:

Background

Pathogenic mutations in WRN are a cause of premature aging disease Werner syndrome (WS). Besides accelerated aging phenotypes and cancer predisposition, patients with WS also display underdevelopment in the skeletal system, characterized by short stature, light body weight and unusually thin extremities. The reasons for these developmental defects are not completely understood and the underlying molecular mechanism remains to be elucidated.

Results

In this study, WRN was found to modulate transcription of short stature homeobox gene SHOX. Loss of WRN resulted in insufficient expression of SHOX, the gene dose of which is critical for driving chondrocyte differentiation. WRN could bind the G-quadruplex (G4) structures in the SHOX promoter and stimulate transcription

SUBMITTER: Leung AO 

PROVIDER: S-EPMC9805690 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature