The TFIID subunit Taf13 is dispensable for RNA polymerase II transcription, but essential for early embryogenesis (RNA-Seq)

RNA polymerase II transcription initiation requires assembly of a preinitiation complex (PIC). According to the stepwise model of PIC assembly, TFIID is the first GTF to be recruited. TFIID comprises TBP and 13 TBP-associated factors (TAFs). We focused on TAF13, the smallest subunit of TFIID. Taf13 has a histone-like domain that heterodimerizes with its partner Taf11. Recently published structures of TFIID place the Taf13-Taf11 heterodimer in lobe A where it forms a “bridge” between TBP and TFIID. According to this structure, the Taf11-Taf13 heterodimer has been suggested to be critical for TBP deposition at promoters. To better address this question, we generated mouse Embryonic Stem Cells (ESCs) cell lines and genetically modified mice where the gene coding for Taf13 was inactivated. Taf13-null mice died at E6.5-E7.5, whereas ESCs survived up to 15 days after inactivation of Taf13, but showed slower growth as compared to controls. In order to understand how inactivation of Taf13 impact the genes expressions we performed bulk mRNA-seq from the Taf13 expressing and null lines. This analysis showed that loss of TAF13 resulted in a greater than two-fold upregulation of 562 genes but only 41 of them were up-regulated more than four-fold. On the other hand, 382 genes were down-regulated, 34 of which showed more than a four-fold repression. Ontology analyses showed that the affected genes did not belong to any specific pathway, but we noticed that many primitive endoderm markers were up-regulated by TAF13 deficiency (Sox7, Sox17, Gata4, Gata6) and some ESC markers were downregulated (Nanog, Klf4, Zfp42) while the pluripotency markers Sox2 and Oct3/4 were unchanged.