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.
Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, 76100, Israel.
Anat
A
Bahat
Ranit
R
Kedmi
Kfir
K
Gazit
Inna
I
Richardo-Lax
Elena
E
Ainbinder
Rivka
R
Dikstein
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D051379:Mice; D009154:Mutation; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D051575:Proto-Oncogene Proteins c-yes / Q000235:genetics / Q000378:metabolism; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics / Q000378:metabolism*; D035362:Transcription Factor TFIID / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D050814:Octamer Transcription Factor-3; D051575:Proto-Oncogene Proteins c-yes; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; C494174:Pou5f1 protein, mouse; C515516:Sohlh2 protein, mouse; C523528:TAF4 protein, mouse; C491103:Taf4b protein, mouse; C496639:Yes1 protein, mouse