Intragenic methylation repatterning is associated with alternative splicing and unique epigenetic phenotypes

Area of Science:

• Plant Molecular Biology
• Epigenetics
• Genomics

Background:

• The role of intragenic cytosine methylation in phenotype determination is debated.
• Previous research linked stress to alternative splicing but lacked genome-wide, single-position analysis.

Purpose of the Study:

• To investigate the functional link between differential DNA methylation and alternative splicing in plants.
• To analyze stress-responsive epigenetic states and heritable memory using the Arabidopsis msh1 system.

Main Methods:

• Utilized the Arabidopsis msh1 mutant system for reproducible epigenetic states.
• Mapped the methylome at single-cytosine resolution using signal detection and machine learning.
• Overlapped differentially methylated genes with msh1-derived transcript isoforms.

Main Results:

• Different patterns of exonic methylation correlated with distinct levels of transcript isoform expression.
• Differentially methylated and alternatively spliced genes were enriched in growth regulators and spliceosome components.
• Targeted genes for differential methylation contained a known CTT motif.

Conclusions:

• Supports a direct association between environmentally responsive differential methylation and alternative splicing in plants.
• Demonstrates how epigenetic modifications can lead to altered phenotypes and heritable stress memory.