Regulation of autophagy by DNA G-quadruplexes

Abstract

ABSTRACT Guanine-rich DNA strands can form secondary structures known as G-quadruplexes (G4-DNA or G4s). G4-DNA is important for the regulation of replication and transcription. We recently showed that the expression of Atg7, a gene that is critical for macroautophagy/autophagy, is controlled by G4-DNA in neurons. We demonstrated that the transcription factor SUB1/PC4 and the G4-DNA-specific antibody HF2 bind to a putative G4-DNA motif located in the Atg7 gene. Stabilizing G4-DNA with the G4-ligand pyridostatin (PDS) downregulates Atg7 expression in neurons. Here, we further investigated how G4-DNA in the Atg7 gene is stabilized by PDS. We show that PDS can form 1:1 and 2:1 complexes with the Atg7’s G4. We also demonstrate that PDS downregulates the ATG7 protein and the expression of Atg7 in astrocytes as well as in neurons. Together with our previous findings, these data establish a novel G4-DNA-associated mechanism of autophagy regulation at a transcriptional level in neurons and astrocytes.