Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300
Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300
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DOI：
10.1016/s0092-8674(00)81165-4
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发表时间：
1998-05-01
期刊：
影响因子：
64.5
通讯作者：
Eckner, R
中科院分区：
文献类型：
--
作者：
Yao, TP;Oh, SP;Eckner, R
转录辅激活因子和整合因子p300及其密切相关的家族成员CBP介导多个信号依赖性转录事件。我们已经产生了缺乏功能性p300基因的小鼠。p300失合子动物在妊娠第9天至第11.5天死亡，表现出神经形成、细胞增殖和心脏发育缺陷。来自p300缺陷胚胎的细胞表现出特定的转录缺陷和增殖不良。令人惊讶的是，p300杂合子也表现出相当大的胚胎致死性。此外，p300和cbp的双杂合性总是与胚胎死亡。因此，小鼠的发育对p300和cbp基因的总剂量非常敏感。我们的研究结果提供了遗传证据，赋予组蛋白乙酰转移酶活性的辅激活因子是哺乳动物细胞增殖和发育所必需的。
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.