PMID:23350932

Citation	Bahat, A, Kedmi, R, Gazit, K, Richardo-Lax, I, Ainbinder, E and Dikstein, R (2013) TAF4b and TAF4 differentially regulate mouse embryonic stem cells maintenance and proliferation. Genes Cells 18:225-37
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 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.
Links	PubMed Online version:10.1111/gtc.12030
Keywords	Animals; Basic Helix-Loop-Helix Transcription Factors/genetics; Basic Helix-Loop-Helix Transcription Factors/metabolism; Cell Cycle/genetics; Cell Line; Cell Proliferation; Embryonic Stem Cells/cytology; Embryonic Stem Cells/metabolism; Gene Expression Regulation; Mice; Mutation; Octamer Transcription Factor-3/genetics; Octamer Transcription Factor-3/metabolism; Protein Binding; Proto-Oncogene Proteins c-yes/genetics; Proto-Oncogene Proteins c-yes/metabolism; TATA-Binding Protein Associated Factors/genetics; TATA-Binding Protein Associated Factors/metabolism; Transcription Factor TFIID/genetics; Transcription Factor TFIID/metabolism; Transcription, Genetic
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:TAF4B		GO:2000648: positive regulation of stem cell proliferation	ECO:0000315:		P		Figure 5 shows transfected mouse embryo cells with TAF4b silenced by siRNAs. Those with silenced TAF4b had lower rates of embryonic cell growth when compared to control.	complete CACAO 9728
MOUSE:TAF4B	involved_in	GO:2000648: positive regulation of stem cell proliferation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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