Gene body-specific methylation on the active X chromosome

Area of Science:

• Epigenetics
• Genomics
• Molecular Biology

Background:

• Differential DNA methylation is crucial for epigenetic gene regulation.
• Allele-specific methylation is known on the inactive X chromosome (Xi) at promoter CpG islands.
• The overall methylation pattern on the active X (Xa) and inactive X (Xi) chromosomes remains largely uncharacterized.

Purpose of the Study:

• To investigate the global methylation patterns on the human active and inactive X chromosomes.
• To determine the distribution and characteristics of allele-specific methylation across the X chromosome.

Main Methods:

• Performed allele-specific analysis at over 1000 informative loci on the human X chromosome.
• Compared methylation patterns between the active X (Xa) and inactive X (Xi) chromosomes.

Main Results:

• The active X chromosome (Xa) exhibits more than double the allele-specific methylation compared to the inactive X (Xi).
• This methylation is predominantly located within gene bodies, affecting numerous adjacent CpGs.
• Prior to X inactivation, these gene body methylation sites were biallelically methylated.

Conclusions:

• A bipartite methylation-demethylation program establishes Xa-specific hypomethylation at promoters and hypermethylation within gene bodies.
• These findings indicate a link between global DNA methylation patterns and gene expression potential on the X chromosome.