N⁶-adenine DNA methylation demystified in eukaryotic genome: From biology to pathology

Area of Science:

• Epigenetics
• Molecular Biology
• Genomics

Background:

• N6-methyl-2 -deoxyadenosine (m6dA) is a known DNA modification in prokaryotes, with recent evidence confirming its presence in eukaryotes.
• m6dA levels appear to decrease with increasing eukaryotic genome complexity.
• Its presence and function in eukaryotes have been a subject of recent investigation.

Purpose of the Study:

• To review the functional importance of m6dA modification in eukaryotic genomes.
• To highlight the roles of m6dA in physiological and pathological processes.
• To discuss the implications of m6dA in gene regulation, development, and disease.

Main Methods:

• Literature review of studies on m6dA in eukaryotic DNA.
• Analysis of m6dA distribution in different eukaryotic genomes (lower and higher eukaryotes).
• Correlation of m6dA levels with developmental stages, diseases (diabetes, cancer), and specific genes (FTO).

Main Results:

• m6dA plays roles in gene regulation and nucleosome positioning in lower eukaryotes.
• In higher eukaryotes, m6dA is enriched in non-genic regions and shows chromosomal bias (e.g., chromosomes X and 13).
• m6dA levels are high during embryogenesis, suggesting a role in development and regeneration, and are decreased in diabetic patients and cancers.

Conclusions:

• m6dA is an important epigenetic modification in eukaryotes with diverse functional roles.
• Dysregulation of m6dA is associated with significant physiological and pathological conditions, including developmental processes and diseases like cancer and diabetes.
• Further research into m6dA mechanisms and its therapeutic potential is warranted.