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GCN5 and p300 share essential functions during early embryogenesis
Author(s) -
Phan Huy M.,
Xu Allison W.,
Coco Cherie,
Srajer Geraldine,
Wyszomierski Shan,
Evrard Yvonne A.,
Eckner Richard,
Dent Sharon Y.R.
Publication year - 2005
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.20445
Subject(s) - biology , pcaf , histone acetyltransferases , p300 cbp transcription factors , phenotype , penetrance , allele , haploinsufficiency , epigenetics , null allele , genetics , histone , conditional gene knockout , embryogenesis , cancer research , embryo , microbiology and biotechnology , gene
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, ∼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. Developmental Dynamics 233:1337–1347, 2005. © 2005 Wiley‐Liss, Inc.