Loss of Gcn5l2 leads to increased apoptosis and mesodermal defects during mouse development

Area of Science:

• Molecular Biology
• Developmental Biology
• Epigenetics

Background:

• Histone acetyltransferases (HATs) regulate gene transcription.
• The roles of specific HATs, like Gcn5, in mammalian development are largely unknown.
• Gcn5 and Pcaf are mouse HATs with shared sequences and activities, interacting with p300/CBP.

Purpose of the Study:

• To investigate the functions of Gcn5 (Gcn5l2) and Pcaf in mammalian embryogenesis.
• To determine the necessity of Gcn5l2 and Pcaf for embryonic development and cell survival.
• To elucidate the specific developmental processes regulated by these histone acetyltransferases.

Main Methods:

• Generation and analysis of Gcn5l2-null and Pcaf-null mouse embryos.
• Phenotypic analysis of embryos at various developmental stages (e.g., 7.5 and 8.5 days post coitum).
• Assessment of cell survival and apoptosis in mutant embryos.

Main Results:

• Pcaf-null mice are viable, indicating Pcaf is dispensable.
• Gcn5l2-null embryos exhibit embryonic lethality due to severe growth retardation and failure to form dorsal mesoderm lineages.
• Apoptosis in Gcn5l2-null embryos precedes morphological abnormalities; combined Gcn5l2 and Pcaf nulls show more severe defects.

Conclusions:

• Gcn5l2 is essential for mammalian embryonic survival and dorsal mesoderm formation.
• Histone acetyltransferases Gcn5l2 and Pcaf have overlapping, yet distinct, roles in embryogenesis.
• Specific HATs are required for cell survival and mesoderm development in mammals.