G-quadruplexes regulate chromatin accessibility and gene expression in Bloom Syndrome

Area of Science:

• Genetics and Molecular Biology
• Genomic Instability Research
• DNA Structure and Function

Background:

• Bloom Syndrome (BS) is a genetic disorder marked by hyper-recombination and genomic instability.
• Mutations in the BLM gene, encoding a RecQ helicase, cause BS.
• DNA G-quadruplexes (G4s) are structures with regulatory roles in gene expression and chromatin organization.

Purpose of the Study:

• To investigate alterations in G4 profiles in Bloom Syndrome.
• To determine the contribution of G4s to BS-associated molecular changes.
• To elucidate the role of BLM helicase in G4 resolution and its impact on genome stability.

Main Methods:

• Chromatin accessibility profiling using ATAC-seq.
• Gene expression analysis using RNA-seq.
• Mapping of endogenous G4 structures via ChIP-seq in wild-type and BS cell lines.

Main Results:

• BS cell lines showed differential G4 formation correlating with altered chromatin accessibility and gene expression.
• G4 stabilization in wild-type cells partially mimicked BS molecular phenotypes.
• Regions with increased chromatin accessibility in BS were enriched for G4 sequences.

Conclusions:

• G4 structures play a significant regulatory role in Bloom Syndrome.
• Unresolved G4s in BLM-deficient cells enhance chromatin accessibility, promoting gene expression.
• BLM's function extends to regulating G4 structures, highlighting their role in BS etiology.