Spatiotemporal DNA methylation dynamics shape megabase-scale methylome landscapes

Area of Science:

• Epigenetics
• Genomics
• Cell Biology

Background:

• DNA methylation is a key epigenetic regulator of cellular reprogramming and development.
• Distinct DNA methylome landscapes exist between human and mouse cells, but the underlying factors are unclear.
• Understanding megabase-scale methylome patterns is crucial for deciphering cellular differentiation.

Purpose of the Study:

• To investigate the factors driving megabase-scale DNA methylation pattern differences across cell types.
• To explore the relationship between genomic region properties and DNA (de)methylation.
• To elucidate how spatial genome organization influences epigenetic regulation.

Main Methods:

• Analysis of 258 human and 301 mouse whole-genome bisulfite sequencing datasets.
• Investigating correlations between genomic region characteristics (GC content, AT content, nuclear location) and DNA methylation states.
• Examining changes in these properties during embryonic and germline reprogramming.

Main Results:

• Genomic regions with high guanine-cytosine (GC) content near the nuclear center are prone to global DNA demethylation and methylation during reprogramming.
• Regions forming partially methylated domains resist demethylation, are adenine-thymine (AT) rich, and associate with the nuclear lamina.
• Spatial properties, influenced by GC content, affect DNA (de)methylation machinery accessibility, shaping methylome patterns.

Conclusions:

• Genomic spatial properties and guanine-cytosine content significantly influence megabase-scale DNA methylation patterns.
• These properties change during cell differentiation, leading to distinct cell-type-specific methylomes.
• Nuclear organization and chromatin accessibility are critical determinants of epigenetic landscapes.