TAF4b and TAF4 differentially regulate mouse embryonic stem cells maintenance and proliferation

Abstract

TAF4b is a cell type-specific subunit of the general transcription factor TFIID. Here, we show that TAF4b is highly expressed in embryonic stem cells (ESC) and is down-regulated upon differentiation. To examine the role of TAF4b in ESC, we applied a knockdown (KD) approach. TAF4b depletion is associated with morphological changes and reduced expression of the selfrenewal marker alkaline phosphatase. In contrast, KD of TAF4, a ubiquitously expressed TAF4b paralog, retained and even stabilized ESC stemness. Retinoic acid-induced differentiation was facilitated in the absence of TAF4b but was significantly delayed by TAF4 KD. Furthermore, TAF4b supports, whereas TAF4 inhibits, ESC proliferation and cell cycle progression. We identified a subset of TAF4b target genes preferentially expressed in ESC and controlling the cell cycle. Among them are the germ cell-specific transcription factor Sohlh2 and the protein kinase Yes1, which was recently shown to regulate ESC self-renewal. Interestingly, Sohlh2 and Yes1 are also targets of the pluripotency factor Oct4, and their regulation by Oct4 is TAF4b-dependent. Consistent with that, TAF4b but not TAF4 interacts with Oct4. Our findings suggest that TAF4b cooperates with Oct4 to regulate a subset of genes in ESC, whereas TAF4 is required for later embryonic developmental stages.

Essential role of the TFIID subunit TAF4 in murine embryogenesis and embryonic stem cell differentiation

“…In contrast, Bahat et al . 44 used siRNA knockdown and reported that Taf4b plays a critical role in maintaining ES cell stemness, whereas Taf4 knockdown had no effect. Thus, there are conflicting data on the role of Taf4 and Taf4b in maintaining ESC pluripotency, perhaps related to the techniques used or the efficiencies of knockdown achieved.…”

Targeting TBP-Associated Factors in Ovarian Cancer

“…Bahat et al recently reported that the TAF4 paralog TAF4B is highly expressed in mESCs and is downregulated upon differentiation (55). We have independently observed the reduction of TAF1, TAF4, TAF4B, and TBP upon in vitro differentiation of mouse embryonic stem cells by RA (Figure 4B).…”

“…Moreover, the Bahat et al study reveals that TAF4B knockdown decreases mESC self-renewal, differentiation, and cell cycle progression, along with a reduction in genes that are also reduced upon RA-induced mESC differentiation. Conversely, they report TAF4 knockdown to increase proliferation and prevent RA-induced differentiation (55), suggesting functional differences between these paralogs in mESCs. Mengus et al report an increase in serum-independent autocrine growth upon TAF4 knockdown in MEFs, which they attribute to compensation by TAF4B (56), suggesting some functional overlap between these paralogs.…”

Separable regulation of POW1 in TAF2-mediated grain development and BR-mediated leaf angle formation in rice

“…A TS mutation in CCG1/TAF1 in hamster cells provokes G 1 /S arrest (Sekiguchi et al, 1991), and TAF9 inactivation in chicken DT40 cells causes cell cycle arrest and apoptosis (Chen and Manley, 2000). Mouse cells that lacked TAF10 were found to be blocked in the G 1 /G 0 phase and underwent apoptosis (Metzger et al, 1999), and a subset of TAF4b-target genes preferentially expressed in embryonic stem cells to be involved in cell cycle control (Bahat et al, 2013). Studies have also indicated that TAFs could interact with specific transcription factors (Reeves and Hahn, 2005; Garbett et al, 2007), transcription activators (Rojo Niersbach et al, 1999; Asahara et al, 2001), and components involved in epigenetic modification (Jacobson et al, 2000; Lindner et al, 2013).…”