Distinct but overlapping roles of histone acetylase PCAF and of the closely related PCAF-B/GCN5 in mouse embryogenesis
Distinct but overlapping roles of histone acetylase PCAF and of the closely related PCAF-B/GCN5 in mouse embryogenesis
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DOI：
10.1073/pnas.97.21.11303
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发表时间：
2000-10-10
影响因子：
11.1
通讯作者：
Nakatani, Y
中科院分区：
文献类型：
--
作者：
Yamauchi, T;Yamauchi, J;Nakatani, Y
PCAF在培养细胞的转录激活、细胞周期阻滞和细胞分化中起作用。PCAF通过其固有的组蛋白乙酰化酶活性乙酰化染色质和转录因子而促进转录激活。在这份报告中，我们提出的证据PCAF和密切相关的PCAF-B/GCN 5的体内功能。缺乏PCAF的小鼠发育正常，没有明显的表型。在PCAF空合子小鼠中，PCAF-B/GCN 5的蛋白水平在肺和肝中急剧升高，其中PCAF在野生型小鼠中大量表达。提示PCAF-B/GCN 5在功能上补偿PCAF。相反，缺乏PCAF-B/GCN 5的动物在妊娠9.5至11.5天之间死亡。正常情况下，PCAF-B/GCN 5 mRNA在第a天已经以高水平表达。而PCAF mRNA在第12.5天首次被检测到，这可以部分解释不同的敲除表型。这些结果提供了证据，表明PCAF和PCAF-B/GCN 5在胚胎发生中发挥不同但功能重叠的作用。
PCAF plays a role in transcriptional activation, cell-cycle arrest, and cell differentiation in cultured cells. PCAF contributes to transcriptional activation by acetylating chromatin and transcription factors through its intrinsic histone acetylase activity. In this report, we present evidence for the in vivo function of PCAF and the closely related PCAF-B/GCN5. Mice lacking PCAF are developmentally normal without a distinct phenotype. In PCAF null-zygous mice, protein levels of PCAF-B/GCN5 are drastically elevated in lung and liver, where PCAF is abundantly expressed in wild-type mice. suggesting that PCAF-B/GCN5 functionally compensates for PCAF. In contrast, animals lacking PCAF-B/GCN5 die between days 9.5 and 11.5 of gestation. Normally, PCAF-B/GCN5 mRNA is expressed at high levels already by day a. whereas PCAF mRNA is first detected on day 12.5, which may explain, in part, the distinct knockout phenotypes, These results provide evidence that PCAF and PCAF-B/GCN5 play distinct but functionally overlapping roles in embryogenesis.