Gene Dosage–Dependent Embryonic Development and Proliferation Defects in Mice Lacking the Transcriptional Integrator p300
Copyright policy )Gene Dosage–Dependent Embryonic Development and Proliferation Defects in Mice Lacking the Transcriptional Integrator p300
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.
- Harvard University United States
- Tufts University United States
- Jackson Laboratory United States
- University of Zurich Switzerland
Heart: em, Heterozygote, Fetal-Development: ge, Brain: ab, ph, Transcription-Genetic, Trans-Activators: ge, Gene Dosage, Neural-Tube-Defects: ge, 610, Receptors-Retinoic-Acid: ge, Nuclear Receptor Coactivator 3, Embryonic and Fetal Development, Mice, Gene-Expression-Regulation-Developmental: ph, SUPPORT-U-S-GOVT-P-H-S, Animals, Neural Tube Defects, Nuclear-Proteins: ge, SUPPORT-NON-U-S-GOVT, Cells, Cultured, Crosses, Genetic, Histone Acetyltransferases, Mice, Knockout, Biochemistry, Genetics and Molecular Biology(all), Mice-Inbred-C57BL, Brain, Gene Expression Regulation, Developmental, Nuclear Proteins, Crosses-Genetic, Gene-Dosage, Heart, Mice-Knockout, Fibroblasts, DNA-Binding Proteins, Mice, Inbred C57BL, Cells-Cultured, CCAAT-Enhancer-Binding Proteins, Cell-Division, Fibroblasts: cy, DNA-Binding-Proteins: ge, Cell Division
Heart: em, Heterozygote, Fetal-Development: ge, Brain: ab, ph, Transcription-Genetic, Trans-Activators: ge, Gene Dosage, Neural-Tube-Defects: ge, 610, Receptors-Retinoic-Acid: ge, Nuclear Receptor Coactivator 3, Embryonic and Fetal Development, Mice, Gene-Expression-Regulation-Developmental: ph, SUPPORT-U-S-GOVT-P-H-S, Animals, Neural Tube Defects, Nuclear-Proteins: ge, SUPPORT-NON-U-S-GOVT, Cells, Cultured, Crosses, Genetic, Histone Acetyltransferases, Mice, Knockout, Biochemistry, Genetics and Molecular Biology(all), Mice-Inbred-C57BL, Brain, Gene Expression Regulation, Developmental, Nuclear Proteins, Crosses-Genetic, Gene-Dosage, Heart, Mice-Knockout, Fibroblasts, DNA-Binding Proteins, Mice, Inbred C57BL, Cells-Cultured, CCAAT-Enhancer-Binding Proteins, Cell-Division, Fibroblasts: cy, DNA-Binding-Proteins: ge, Cell Division
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