Histone H3-K9 methyltransferase ESET is essential for early development

Area of Science:

• Epigenetics
• Developmental Biology
• Molecular Biology

Background:

• Histone H3 lysine 9 (H3-K9) methylation is crucial for heterochromatin formation and gene silencing.
• Histone methyltransferases like ESET, G9a, and SUV39-h catalyze H3-K9 methylation in mammals.
• Previous studies show roles for SUV39-h in heterochromatin and G9a in euchromatic gene silencing, with distinct developmental impacts.

Purpose of the Study:

• To investigate the in vivo function of ESET, a histone methyltransferase.
• To understand ESET's role in early mouse development and embryonic stem cell survival.

Main Methods:

• Generation of a knockout mouse model lacking ESET pre- and post-SET domains, using lacZ as a reporter.
• Analysis of zygotic and maternal ESET expression patterns during mouse development.
• Phenotypic analysis of homozygous ESET-mutant embryos and blastocysts, including in vitro culture of embryonic stem cells.

Main Results:

• Homozygous ESET mutations lead to peri-implantation lethality between 3.5 and 5.5 days postcoitum.
• ESET-null blastocysts showed defective inner cell mass growth and failed to establish embryonic stem cell lines.
• Global H3-K9 trimethylation and DNA methylation in IAP repeats were not significantly altered in ESET-null blastocysts.

Conclusions:

• ESET is essential for peri-implantation development in mice.
• ESET is required for the survival and proliferation of embryonic stem cells.
• The essential function of ESET in early development may not solely rely on global H3-K9 trimethylation or DNA methylation of IAP repeats.