TAF 4b and TAF 4 differentially regulate mouse embryonic stem cells maintenance and proliferation

TAF 4b is a cell type‐specific subunit of the general transcription factor TFIID . Here, we show that TAF 4b is highly expressed in embryonic stem cells ( ESC ) and is down‐regulated upon differentiation. To examine the role of TAF 4b in ESC , we applied a knockdown ( KD ) approach. TAF 4b depletion is associated with morphological changes and reduced expression of the self‐renewal marker alkaline phosphatase. In contrast, KD of TAF 4, a ubiquitously expressed TAF 4b paralog, retained and even stabilized ESC stemness. Retinoic acid‐induced differentiation was facilitated in the absence of TAF 4b but was significantly delayed by TAF 4 KD . Furthermore, TAF 4b supports, whereas TAF 4 inhibits, ESC proliferation and cell cycle progression. We identified a subset of TAF 4b target genes preferentially expressed in ESC and controlling the cell cycle. Among them are the germ cell‐specific transcription factor S ohlh2 and the protein kinase Y es1, which was recently shown to regulate ESC self‐renewal. Interestingly, S ohlh2 and Y es1 are also targets of the pluripotency factor O ct4, and their regulation by O ct4 is TAF 4b‐dependent. Consistent with that, TAF 4b but not TAF 4 interacts with O ct4. Our findings suggest that TAF 4b cooperates with O ct4 to regulate a subset of genes in ESC , whereas TAF 4 is required for later embryonic developmental stages.