PMID- 23350932 OWN - NLM STAT- MEDLINE DCOM- 20130805 LR - 20130225 IS - 1365-2443 (Electronic) IS - 1356-9597 (Linking) VI - 18 IP - 3 DP - 2013 Mar TI - TAF4b and TAF4 differentially regulate mouse embryonic stem cells maintenance and proliferation. PG - 225-37 LID - 10.1111/gtc.12030 [doi] AB - 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. CI - (c) 2013 The Authors Genes to Cells (c) 2013 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd. FAU - Bahat, Anat AU - Bahat A AD - Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, 76100, Israel. FAU - Kedmi, Ranit AU - Kedmi R FAU - Gazit, Kfir AU - Gazit K FAU - Richardo-Lax, Inna AU - Richardo-Lax I FAU - Ainbinder, Elena AU - Ainbinder E FAU - Dikstein, Rivka AU - Dikstein R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130127 PL - England TA - Genes Cells JT - Genes to cells : devoted to molecular & cellular mechanisms JID - 9607379 RN - 0 (Basic Helix-Loop-Helix Transcription Factors) RN - 0 (Octamer Transcription Factor-3) RN - 0 (Pou5f1 protein, mouse) RN - 0 (Sohlh2 protein, mouse) RN - 0 (TAF4 protein, mouse) RN - 0 (TATA-Binding Protein Associated Factors) RN - 0 (Taf4b protein, mouse) RN - 0 (Transcription Factor TFIID) RN - EC 2.7.10.2 (Proto-Oncogene Proteins c-yes) RN - EC 2.7.10.2 (Yes1 protein, mouse) SB - IM MH - Animals MH - Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism MH - Cell Cycle/genetics MH - Cell Line MH - *Cell Proliferation MH - Embryonic Stem Cells/cytology/*metabolism MH - *Gene Expression Regulation MH - Mice MH - Mutation MH - Octamer Transcription Factor-3/genetics/metabolism MH - Protein Binding MH - Proto-Oncogene Proteins c-yes/genetics/metabolism MH - TATA-Binding Protein Associated Factors/genetics/*metabolism MH - Transcription Factor TFIID/genetics/*metabolism MH - Transcription, Genetic EDAT- 2013/01/29 06:00 MHDA- 2013/08/06 06:00 CRDT- 2013/01/29 06:00 PHST- 2012/03/13 00:00 [received] PHST- 2012/12/05 00:00 [accepted] PHST- 2013/01/29 06:00 [entrez] PHST- 2013/01/29 06:00 [pubmed] PHST- 2013/08/06 06:00 [medline] AID - 10.1111/gtc.12030 [doi] PST - ppublish SO - Genes Cells. 2013 Mar;18(3):225-37. doi: 10.1111/gtc.12030. Epub 2013 Jan 27.