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PMID:15937931

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Citation

Phan, HM, Xu, AW, Coco, C, Srajer, G, Wyszomierski, S, Evrard, YA, Eckner, R and Dent, SY (2005) GCN5 and p300 share essential functions during early embryogenesis. Dev. Dyn. 233:1337-47

Abstract

Previous studies revealed that deletion of genes encoding the histone acetyltransferases GCN5, p300, or CBP results in embryonic lethality in mice. PCAF and GCN5 physically interact with p300 and CBP in vitro. To determine whether these two groups of histone acetyltransferases interact functionally in vivo, we created mice lacking one or more alleles of p300, GCN5, or PCAF. As expected, we found that mice heterozygous for any single null allele are viable. The majority of GCN5(+/-)p300(+/-) mice also survive to adulthood with no apparent abnormalities. However, approximately 25% of these mice die before birth. These embryos are developmentally stunted and exhibit increased apoptosis compared with wild-type or single GCN5(+/-) or p300(+/-) littermates at embryonic day 8.5. In contrast, no abnormalities were observed in PCAF(-/-) p300(+/-) mice. Of interest, we find that p300 protein levels vary in different mouse genetic backgrounds, which likely contributes to the incomplete penetrance of the abnormal phenotype of GCN5(+/-) p300(+/-) mice. Our data indicate that p300 cooperates specifically with GCN5 to provide essential functions during early embryogenesis.

Links

PubMed Online version:10.1002/dvdy.20445

Keywords

Animals; Apoptosis/genetics; Cell Cycle Proteins/genetics; Cell Cycle Proteins/physiology; Cell Lineage/genetics; Cell Lineage/physiology; Embryo, Mammalian/physiology; Genes, Lethal; Heterozygote; Histone Acetyltransferases/genetics; Histone Acetyltransferases/physiology; Mice; Mice, Inbred Strains; Mice, Knockout; Transcription Factors/genetics; Transcription Factors/physiology; p300-CBP Transcription Factors

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

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