Format

Send to

Choose Destination
Cell. 1998 May 1;93(3):361-72.

Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300.

Author information

1
Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.

Abstract

The transcriptional coactivator and integrator p300 and its closely related family member CBP mediate multiple, signal-dependent transcriptional events. We have generated mice lacking a functional p300 gene. Animals nullizygous for p300 died between days 9 and 11.5 of gestation, exhibiting defects in neurulation, cell proliferation, and heart development. Cells derived from p300-deficient embryos displayed specific transcriptional defects and proliferated poorly. Surprisingly, p300 heterozygotes also manifested considerable embryonic lethality. Moreover, double heterozygosity for p300 and cbp was invariably associated with embryonic death. Thus, mouse development is exquisitely sensitive to the overall gene dosage of p300 and cbp. Our results provide genetic evidence that a coactivator endowed with histone acetyltransferase activity is essential for mammalian cell proliferation and development.

PMID:
9590171
DOI:
10.1016/s0092-8674(00)81165-4
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center