Mohan William S, Scheer Elisabeth, Wendling Olivia, Metzger Daniel, Tora Làszlò
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, F-67404 Illkirch Cedex, CU de Strasbourg, France.
Mol Cell Biol. 2003 Jun;23(12):4307-18. doi: 10.1128/MCB.23.12.4307-4318.2003.
TAF10 (formerly TAF(II)30), is a component of TFIID and the TATA box-binding protein (TBP)-free TAF-containing complexes (TFTC/PCAF/STAGA). To investigate the physiological function of TAF10, we disrupted its gene in mice by using a Cre recombinase/LoxP strategy. Interestingly, no TAF10(-/-) animals were born from intercrosses of TAF10(+/-) mice, indicating that TAF10 is required for embryogenesis. TAF10(-/-) embryos developed to the blastocyst stage, implanted, but died shortly after ca. 5.5 days postcoitus. Surprisingly, trophoblast cells from TAF10(-/-) blastocysts were viable, whereas inner cell mass cells failed to survive, highlighting that TAF10 is not generally required for transcription in all cells. TAF10-deficient cells express normal levels of TBP and TAFs other than TAF10 but contain only partially formed TFIID, are endocycle arrested, and have undetectable levels of transcription. Thus, our results demonstrate that TAF10 is required for TFIID stability, cell cycle progression, and transcription in the early mouse embryo.
TAF10(以前称为TAF(II)30)是TFIID以及不含TATA盒结合蛋白(TBP)的含TAF复合物(TFTC/PCAF/STAGA)的一个组成部分。为了研究TAF10的生理功能,我们通过使用Cre重组酶/LoxP策略在小鼠中破坏了它的基因。有趣的是,TAF10(+/-)小鼠杂交后代中没有TAF10(-/-)动物出生,这表明TAF10是胚胎发育所必需的。TAF10(-/-)胚胎发育到囊胚阶段,着床,但在交配后约5.5天左右不久死亡。令人惊讶的是,TAF10(-/-)囊胚的滋养层细胞是有活力的,而内细胞团细胞未能存活,这突出表明TAF10并非在所有细胞的转录中普遍必需。缺乏TAF10的细胞表达正常水平的TBP以及除TAF10之外的其他TAF,但仅含有部分形成的TFIID,细胞内复制停滞,并且转录水平检测不到。因此,我们的结果表明TAF10是小鼠早期胚胎中TFIID稳定性、细胞周期进程和转录所必需的。