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

First Author  Yao TP Year  1998
Journal  Cell Volume  93
Issue  3 Pages  361-72
PubMed ID  9590171 Mgi Jnum  J:47301
Mgi Id  MGI:1203276 Doi  10.1016/s0092-8674(00)81165-4
Citation  Yao TP, et al. (1998) Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300. Cell 93(3):361-72
abstractText  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.
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