Sustained Epigenetic Reactivation in Fragile X Neurons with an RNA-Binding Small Molecule.

ABSTRACT:

Background/objectives

Fragile X syndrome (FXS) is a disease of pathologic epigenetic silencing induced by RNA. In FXS, an expanded CGG repeat tract in the FMR1 gene induces epigenetic silencing during embryogenesis. FMR1 silencing can be reversed with 5-aza-deoxyctidine (5-aza-dC), a nonspecific epigenetic reactivator; however, continuous administration of 5-aza-dC is problematic due to its toxicity. We describe an approach to restore FMR1 expression in FXS neurons by transient treatment with 5-aza-dC, followed by treatment with 2HE-5NMe, which binds the CGG repeat expansion in the FMR1 mRNA and could block the resilencing of the FMR1 gene after withdrawal of 5-aza-dC.

Methods

This study uses immunofluorescence and fluorescent in situ hybri

SUBMITTER: Kam CW 

PROVIDER: S-EPMC11942054 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature