Isogenic mice exhibit sexually-dimorphic DNA methylation patterns across multiple tissues

Area of Science:

• Epigenetics
• Genomics
• Molecular Biology

Background:

• Cytosine methylation is a key epigenetic modification influencing physiology and disease.
• Sexual dimorphism is common in diseases, but sex-based epigenetic influences are poorly understood.

Purpose of the Study:

• To investigate DNA methylation patterns in male and female mice across multiple tissues.
• To identify sex-specific epigenetic variations and their tissue-specific characteristics.

Main Methods:

• Reduced representation bisulphite sequencing (RRBS) was performed on liver, heart, brain, muscle, and spleen tissues from isogenic male and female mice.
• Analysis of DNA methylation patterns to identify sexually dimorphic loci.

Main Results:

• Thousands of sexually dimorphic DNA methylation loci were identified across tissues.
• Methylation differences were largely tissue-autonomous, with females often showing hypermethylation compared to males.
• Affected loci were enriched in ontologies related to tissue function, with some differences independent of testosterone.

Conclusions:

• Epigenetic states exhibit tissue-specific gender differences, potentially independent of sex hormones.
• These gender-specific epigenetic patterns have significant implications for understanding sex differences in health and disease phenotypes.