GCN5 and p300 share essential functions during early embryogenesis.
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.
Phan
Huy M
HM
Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Xu
Allison W
AW
Coco
Cherie
C
Srajer
Geraldine
G
Wyszomierski
Shannon
S
Evrard
Yvonne A
YA
Eckner
Richard
R
Dent
Sharon Y R
SY
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000502:physiology; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology; D004622:Embryo, Mammalian / Q000502:physiology*; D005804:Genes, Lethal; D006579:Heterozygote; D051548:Histone Acetyltransferases / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D018797:Cell Cycle Proteins; D051548:Histone Acetyltransferases; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor