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The polycomb-group gene Ezh2 is required for early mouse development.
D O'Carroll1, S Erhardt, M Pagani
1Research Institute of Molecular Pathology (IMP), A-1030 Vienna, Austria.
Molecular and Cellular Biology
|June 8, 2001
Summary
Polycomb gene Enhancer of zeste homolog 2 (Ezh2) is crucial for early mouse development. Ezh2 deficiency causes lethality post-implantation, highlighting its essential role in embryonic development.
Area of Science:
- Developmental Biology
- Epigenetics
- Genetics
Background:
- Polycomb-group (Pc-G) genes regulate gene expression through chromatin modification.
- Enhancer of zeste homolog 2 (Ezh2) is a highly conserved Pc-G gene with a SET domain, potentially involved in histone methyltransferase activity.
- Ezh2 is part of a histone deacetylase complex and its in vivo function in mammals is largely unknown.
Purpose of the Study:
- To investigate the in vivo function of Ezh2 during early mouse development.
- To determine the consequences of Ezh2 deficiency in mice.
Main Methods:
- Generation of Ezh2-deficient mice.
- Analysis of embryonic development in Ezh2 mutant mice.
- Assessment of blastocyst outgrowth and embryonic stem cell establishment.
Main Results:
- Ezh2 null mutation leads to early embryonic lethality, with development ceasing after implantation or failing during gastrulation.
- Ezh2-deficient blastocysts exhibit impaired outgrowth, preventing the generation of Ezh2-null embryonic stem cells.
- Ezh2 expression is upregulated upon fertilization and maintained at high levels during preimplantation stages.
Conclusions:
- Ezh2 plays an essential and indispensable role in early mouse development.
- Ezh2 genetically links with other early-acting Pc-G genes, eed and YY1.
- The findings establish a critical function for Ezh2 in embryonic progression and Pc-G gene regulation.