G9a/GLP Complex Maintains Imprinted DNA Methylation in Embryonic Stem Cells

Area of Science:

• Epigenetics
• Genomics
• Gene Regulation

Background:

• Genomic imprinting ensures monoallelic gene expression through sex-specific DNA methylation at imprinting control regions (ICRs).
• ICRs are also marked by allele-specific histone modifications, but their role in imprinting maintenance is unclear.

Purpose of the Study:

• To investigate the role of histone H3 lysine 9 methyltransferases (HMTs), specifically G9a and GLP, in maintaining DNA methylation at ICRs.

Main Methods:

• Utilized embryonic stem cells with depleted G9a and GLP.
• Assessed DNA methylation and histone modification patterns at ICRs.
• Investigated the interaction between G9a/GLP, DNA methyltransferases, and TET dioxygenases.

Main Results:

• G9a and GLP are essential for stable maintenance of imprinted DNA methylation in embryonic stem cells.
• The catalytic activity of G9a/GLP and the resulting H3K9me2 mark are dispensable for imprinting maintenance.
• G9a/GLP protects imprinted DNA methylation by recruiting de novo DNA methyltransferases, counteracting TET dioxygenase activity.

Conclusions:

• The G9a/GLP complex plays a critical role in preserving imprinted DNA methylation, independent of its catalytic H3K9me2 mark.
• This protection mechanism involves the recruitment of DNA methyltransferases to antagonize DNA methylation erosion by TET enzymes.