Mammalian TAF(II)30 is required for cell cycle progression and specific cellular differentiation programmes.
The two alleles of the 30 kDa TATA-binding protein associated factor (TAF(II)30) gene, have been targeted by homologous recombination in murine F9 embryonal carcinoma cells and subsequently disrupted using a Cre recombinase-loxP strategy. The TAF(II)30-null cells are not viable, but are rescued by the expression of human TAF(II)30. Cells lacking TAF(II)30 are blocked in G(1)/G(0) phase of the cell cycle and undergo apoptosis. In agreement with the G(1) arrest phenotype, the expression of cyclin E is impaired and the retinoblastoma protein is hypophosphorylated in the TAF(II)30-null cells. Interestingly, retinoic acid (RA) treatment prevented TAF(II)30-null cell death and induced primitive endodermal differentiation. In contrast, the RA- and cAMP-induced parietal endodermal differentiation was impaired in the TAF(II)30-null cells. Thus, TAF(II)30 is not indispensable for class II gene transcription in general, but seems to be required for the expression of a subset of genes.
Metzger
D
D
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Collège de France, BP 163-67404 Illkirch Cedex, CU de Strasbourg, France.
Scheer
E
E
Soldatov
A
A
Tora
L
L
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D018236:Carcinoma, Embryonal / Q000235:genetics; D002453:Cell Cycle / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D019426:Integrases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D016254:Mutagenesis, Insertional; D013234:Stem Cells / Q000166:cytology; D035381:TATA-Binding Protein Associated Factors; D013997:Time Factors; D035362:Transcription Factor TFIID; D014157:Transcription Factors / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014764:Viral Proteins
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C089768:TAF10 protein, human; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D014764:Viral Proteins; D014212:Tretinoin; C045073:Cre recombinase; D019426:Integrases