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GCN5 and p300 share essential functions during early embryogenesis
Huy M Phan1, Allison W Xu, Cherie Coco
1Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Summary
Histone acetyltransferases p300 and GCN5 cooperate during early embryogenesis. Deleting both genes in mice causes developmental defects and embryonic lethality, highlighting their essential functions.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- Histone acetyltransferases (HATs) like GCN5, p300, CBP, and PCAF are crucial for gene regulation.
- Previous studies indicated embryonic lethality upon deletion of GCN5, p300, or CBP genes.
- GCN5 and PCAF are known to interact with p300 and CBP in vitro.
Purpose of the Study:
- To investigate the in vivo functional interactions between histone acetyltransferases p300, GCN5, and PCAF.
- To determine the role of these HATs in early embryonic development.
Main Methods:
- Generation of genetically modified mice lacking one or more alleles of p300, GCN5, or PCAF.
- Phenotypic analysis of resulting mouse embryos at different developmental stages.
- Assessment of apoptosis levels in embryonic tissues.
Main Results:
- Mice heterozygous for single null alleles of p300, GCN5, or PCAF were viable.
- Approximately 25% of GCN5(+/-)p300(+/-) mice exhibited embryonic lethality with developmental stunting and increased apoptosis.
- No abnormalities were observed in PCAF(-/-)p300(+/-) mice.
- p300 protein levels showed variability across different mouse genetic backgrounds, influencing phenotype penetrance.
Conclusions:
- p300 cooperates specifically with GCN5 to fulfill essential functions during early embryogenesis.
- The interaction between p300 and GCN5 is critical for normal embryonic development.
- Genetic background influences the phenotypic outcome of HAT gene deletions.