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ABSTRACT: Apoptotic cell death is associated with altered levels of mRNA expression, yet the mechanisms that coordinate changes in gene expression with activation of the cell death machinery remain obscure. Here, we report the cloning and characterization of hTAF(II)80 delta, a specialized isoform of the general transcription factor TFIID subunit hTAF(II)80. Several distinct apoptotic stimuli induce the expression and caspase-dependent cleavage of hTAF(II)80 delta. hTAF(II)80 delta, unlike hTAF(II)80, forms a TFIID-like complex lacking hTAF(II)31. Elevated expression of hTAF(II)80 delta in HeLa cells is sufficient to trigger apoptotic cell death and selectively alters cellular transcription, including the induction of the target genes gadd45 and p21. These data define a signaling pathway that couples apoptotic signals to a reprogramming of RNA polymerase II transcription.
Molecular Cell 10/2001; 8(3):591-600. · 14.18 Impact Factor
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ABSTRACT: 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.
The EMBO Journal 10/1999; 18(17):4823-34. · 9.20 Impact Factor
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ABSTRACT: The basal RNA polymerase II transcription factor, TFIID, is composed of the TATA binding protein (TBP) and 8-13 TBP-associated factors (TAFs) ranging from 250 to 17 kDa. The structure of the human gene encoding the 30-kDa subunit of TFIID, TAF2H, has been determined. The gene consists of five exons (ranging from 66 to 248 bp) and four introns (ranging from 83 to 211 bp). The transcription start site of the mRNA was mapped, and it shares a weak homology to the consensus of known initiator elements. Using in situ hybridization on human metaphase chromosomes, the TAF2H gene has been localized in the 11p15.2-p15.5 region of the human genome.
Genomics 10/1995; 29(1):269-72. · 3.02 Impact Factor
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ABSTRACT: The estrogen receptor (ER) contains two nonacidic transcriptional activation functions, AF-1 and AF-2 (formerly TAF-1 and TAF-2). In this study we show that AF-1 and AF-2 are able to stimulate transcription in vitro in a HeLa cell system when fused to the DNA binding domain of the yeast activator GAL4. We also demonstrate that a factor(s) required for the function of the ER AFs is chromatographically separable from a factor(s) necessary for the activity of the acidic activation domain of VP16. Moreover, immunoprecipitation experiments using a monoclonal antibody directed against the TATA box binding protein (TBP) indicate, that these different factors are associated with TBP in distinct TFIID complexes.
Nucleic Acids Research 02/1993; 21(1):5-12. · 8.03 Impact Factor
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ABSTRACT: We have previously shown that the two transcriptional activation functions (TAF-1 and TAF-2) of the human estrogen receptor (hER) have synergistic properties different from one another and from those of acidic activating domains (AADs). Here we compare the transcriptional interference/squelching properties of the hER TAFs with those of the AADs of yeast GAL4 and chimeric GAL-VP16 activators. Our results indicate that AADs interact with a factor(s) that, while required for activation by AADs, is not essential for activation by hER TAFs. In contrast, hER TAFs appear to interact with factors indispensable for mediating both their activation function and that of AADs. Thus, different classes of trans-activators may interact with different factors. In addition, the synergistic and transcriptional interference/squelching properties of the two TAFs of the human glucocorticoid receptor (hGR) indicate that both are composed of acidic and nonacidic activation functions.
Cell 10/1990; 62(6):1177-87. · 32.40 Impact Factor
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ABSTRACT: We have previously reported the presence of a hormone-inducible transcriptional activation function (TAF-2) within the region of the estrogen receptor (ER) that contains the hormone binding domain. We show here that the N-terminal A/B region of the ER contains an independent constitutive activation function (TAF-1) that exhibits cell type specificity since it activates transcription efficiently in chicken embryo fibroblasts, but only poorly in HeLa cells. By analyzing the ability of TAF-1, TAF-2, and the GAL4 and VP16 acidic activating domains (AADs) to homosynergize and heterosynergize with one another and with the factor binding to the upstream element (UE) of the adenovirus 2 major late promoter, we show that the activation properties of TAF-1 and TAF-2 are different and distinct from those of AADs, in agreement with the absence of acidic amino acid stretches in TAF-1 and TAF-2.
Cell 12/1989; 59(3):477-87. · 32.40 Impact Factor
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