TATA-binding Associated Factors have distinct roles during early mammalian development

Early embryonic development is a finely orchestrated process that requires precise regulation of gene expression coordinated with morphogenetic events. TATA-box binding protein-associated factors (TAFs), integral components of transcription initiation coactivators like TFIID and SAGA, play a crucial role in this intricate process. Here we show that disruptions in TAF5, TAF12 and TAF13 individually lead to embryonic lethality in the mouse, resulting in overlapping yet distinct phenotypes. Taf5 and Taf12 mutant embryos exhibited a failure to implant post-blastocyst formation, and Taf5 mutants have aberrant lineage specification within the inner cell mass. In contrast, Taf13 mutant embryos successfully implant and form egg-cylinder stages but fail to initiate gastrulation. Strikingly, we observed a depletion of pluripotency factors in TAF13-deficient embryos, including OCT4, NANOG and SOX2, highlighting an indispensable role of TAF13 in maintaining pluripotency. Transcriptomic analysis revealed distinct gene targets affected by the loss of TAF5, TAF12 and TAF13. Thus, we propose that TAF5, TAF12 and TAF13 convey locus specificity to the TFIID complex throughout the mouse genome. Comparative gene expression profiling analysis of RNA-seq data for mouse embryos from a WT, Taf5KO, Taf12KO, or Taf13KO transgenic background.早期胚胎发育是一项高度协同的精密调控过程，需要基因表达的精准调控与形态发生事件相互配合。TATA盒结合蛋白相关因子（TATA-box binding protein-associated factors，TAFs）是转录起始辅激活因子（如TFIID与SAGA）的核心组成部分，在这一复杂过程中发挥关键作用。 本研究证实，TAF5、TAF12与TAF13的单基因功能缺失均会导致小鼠胚胎致死，并引发重叠但各具特征的表型。Taf5与Taf12突变胚胎在囊胚形成后无法完成着床，且Taf5突变胚胎的内细胞团存在异常的谱系特化。与之相反，Taf13突变胚胎可顺利着床并形成卵圆筒期结构，但无法启动原肠胚形成。值得注意的是，我们在TAF13缺陷胚胎中观察到包括OCT4、NANOG与SOX2在内的多能性因子表达耗竭，这凸显了TAF13在维持细胞多能性过程中不可或缺的作用。 转录组分析显示，TAF5、TAF12与TAF13的缺失会影响不同的基因靶标。据此我们提出，TAF5、TAF12与TAF13可为小鼠全基因组范围内的TFIID复合物传递位点特异性。本研究针对野生型（WT）、Taf5敲除（Taf5KO）、Taf12敲除（Taf12KO）及Taf13敲除（Taf13KO）转基因背景的小鼠胚胎，开展了RNA测序（RNA-seq）数据的比较基因表达谱分析。