Bardot Paul, Vincent Stéphane D, Fournier Marjorie, Hubaud Alexis, Joint Mathilde, Tora László, Pourquié Olivier
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch 67400, France.
Centre National de la Recherche Scientifique, UMR7104, Illkirch 67400, France.
Development. 2017 Oct 15;144(20):3808-3818. doi: 10.1242/dev.146902. Epub 2017 Sep 11.
During development, tightly regulated gene expression programs control cell fate and patterning. A key regulatory step in eukaryotic transcription is the assembly of the pre-initiation complex (PIC) at promoters. PIC assembly has mainly been studied , and little is known about its composition during development. data suggest that TFIID is the general transcription factor that nucleates PIC formation at promoters. Here we show that TAF10, a subunit of TFIID and of the transcriptional co-activator SAGA, is required for the assembly of these complexes in the mouse embryo. We performed conditional deletions during mesoderm development and show that loss in the presomitic mesoderm (PSM) does not prevent cyclic gene transcription or PSM segmental patterning, whereas lateral plate differentiation is profoundly altered. During this period, global mRNA levels are unchanged in the PSM, with only a minor subset of genes dysregulated. Together, our data strongly suggest that the TAF10-containing canonical TFIID and SAGA complexes are dispensable for early paraxial mesoderm development, arguing against the generic role in transcription proposed for these fully assembled holo-complexes.
在发育过程中，严格调控的基因表达程序控制着细胞命运和模式形成。真核转录中的一个关键调控步骤是在启动子处组装前起始复合物（PIC）。PIC组装主要已被研究，而关于其在发育过程中的组成知之甚少。数据表明TFIID是在启动子处引发PIC形成的通用转录因子。在这里，我们表明TAF10是TFIID和转录共激活因子SAGA的一个亚基，是小鼠胚胎中这些复合物组装所必需的。我们在中胚层发育过程中进行了条件性缺失，并表明在体节中胚层（PSM）中的缺失并不妨碍周期性基因转录或PSM节段模式形成，而侧板分化则受到深刻改变。在此期间，PSM中的全局mRNA水平不变，只有一小部分基因失调。总之，我们的数据强烈表明，含TAF10的经典TFIID和SAGA复合物对于早期轴旁中胚层发育是可有可无的，这与为这些完全组装的全复合物所提出的在转录中的一般作用相矛盾。
