G-quadruplexes regulate chromatin accessibility and gene expression in Bloom Syndrome [ATAC-seq]

It is caused by mutations in the conserved RecQ helicase gene, BLM, which is essential in maintaining genome integrity and unwinds various aberrant DNA structures. One such structure is DNA G-quadruplexes (G4s), which have broad regulatory functions.

Although putative G4-forming sequences have been previously implicated in BS, it remains unclear what (dys)regulatory role, if any, endogenous G4 structures may play in BS. Here, we profiled chromatin accessibility and gene expression via ATAC-seq and RNA-seq and mapped endogenous G4 via ChIP-seq in wild-type (WT) vs. BS cell lines. We observed that in BS, differential G4 formation positively correlated with both chromatin accessibility and gene expression.