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

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 self-renewal 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.