Yamauchi T, Yamauchi J, Kuwata T, Tamura T, Yamashita T, Bae N, Westphal H, Ozato K, Nakatani Y
Laboratories of Molecular Growth Regulation and Integrative and Medical Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11303-6. doi: 10.1073/pnas.97.21.11303.
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 8, 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.
PCAF在培养细胞的转录激活、细胞周期停滞和细胞分化中发挥作用。PCAF通过其内在的组蛋白乙酰转移酶活性使染色质和转录因子乙酰化，从而促进转录激活。在本报告中，我们提供了PCAF以及与之密切相关的PCAF - B/GCN5体内功能的证据。缺乏PCAF的小鼠发育正常，没有明显的表型。在PCAF纯合缺失小鼠中，PCAF - B/GCN5的蛋白水平在肺和肝脏中显著升高，而在野生型小鼠中PCAF在这些组织中大量表达，这表明PCAF - B/GCN5在功能上补偿了PCAF。相反，缺乏PCAF - B/GCN5的动物在妊娠第9.5天至11.5天之间死亡。正常情况下，PCAF - B/GCN5 mRNA在第8天就已经高水平表达，而PCAF mRNA在第12.5天才首次检测到，这可能部分解释了不同的基因敲除表型。这些结果提供了证据，表明PCAF和PCAF - B/GCN5在胚胎发生中发挥着不同但功能重叠的作用。
