DNA methylation dynamics and dysregulation delineated by high-throughput profiling in the mouse

Area of Science:

• Epigenetics and genomics
• Mammalian molecular biology

Background:

• DNA methylation is crucial for mammalian development and disease.
• Comprehensive epigenomic atlases are essential for understanding complex biological processes.

Purpose of the Study:

• To develop a high-throughput mouse DNA methylation array.
• To create a reference mouse methylation atlas for diverse biological contexts.
• To explore DNA methylation dynamics in differentiation, aging, and tumorigenesis.

Main Methods:

• Development of the Infinium Mouse Methylation BeadChip (MM285) with 296,070 probes.
• Generation of a mouse methylation atlas from 1,239 DNA samples (tissues, strains, ages, sexes, pathologies).
• Bioinformatic analysis of methylation patterns and their association with biological variables.

Main Results:

• Tissue-specific methylation signatures correlate with transcription factor binding sites.
• Age-associated DNA hypermethylation occurs at Polycomb-repressed regions; hypomethylation at cohesin-bound regions.
• Apc polyp-associated hypermethylation affects intestinal differentiation enhancers; hypomethylation targets AP-1 sites.

Conclusions:

• The mouse methylation array and atlas provide a valuable resource for epigenomic research.
• DNA methylation patterns are intricately linked to cellular identity, aging, and cancer development.
• This platform will accelerate high-throughput epigenomic studies in the mouse model organism.