Single-Molecule Nanopore Sequencing of the CpG Island from the Promoter of O6-Methylguanine-DNA Methyltransferase Provides Insights into the Mechanism of De Novo Methylation of G/C-Rich Regions.

ABSTRACT:

Background

The methylation of cytosine residues at CpG sites within the O6-methylguanine-DNA methyltransferase (MGMT) promoter is a key biomarker in glioblastoma therapy. The MGMT promoter (MGMTp) contains multiple guanine-rich sequences capable of folding into G-quadruplexes (G4s), but their relevance for MGMTp methylation is poorly understood.

Objectives

Our study explores the impact of potential G-quadruplex-forming sequences (PQS) in the MGMT promoter CpG island on the activity of de novo DNA methyltransferase Dnmt3a. Additionally, we investigate their influence on the accuracy of methylation pattern detection using nanopore sequencing.

Methods

Nanopore sequencing was employed to analyze the methylation of 94 clinically significant CpG sites i

SUBMITTER: Sergeev AV 

PROVIDER: S-EPMC11843895 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature