[Analysis of the mechanism of transcriptional regulation based on yeast system].
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Animals↗
Biomedical subjects
M Horikoshi
Publications and source records attributed to M Horikoshi.
[Retroperitoneal fibrosis with involvement up to the mediastinal space].
A 60-year-old man presented with sudden palpitations in September 1993, and was admitted to hospital with a diagnosis of atrial fibrillation and heart failure. The patient was suspected of having collagen disease, because of a positive test for antinuclear antibodies and a high sedimentation rate. He was referred to lou hospital. Chest radiographic findings were suggestive of cardiomegaly and cardiac murmurs were audible, which indicated the presence of heart disease. A chest Ct scan revealed a lesion surrounding the intramediastinal large vessels and the heart from the level of the confluence of the left brachiocephalic vein and the superior vena cava. Suspicion of a mediastinal tumor led the patient to be admitted to the respiratory department. Percutaneous needle biopsy with a Trucut needle revealed non-specific chronic inflammation. An abdominal CT scan showed that the lesion surrounding the descending aorta traversed the diaphragm, reached the renal pelvis along both renal arteries, and caused narrowing of the ureter and left hydronephrosis. Based on these findings, retroperitoneal fibrosis was diagnosed. Treatment with steroids caused the lesion to shrink.
Anti-Inflammatory Agents↗
Isolation and characterization of a cDNA encoding a new type of human transcription elongation factor S-II.
We report the isolation of a cDNA encoding a new type of transcription factor S-II, termed h-SII-T1, from a human library. The mRNA corresponding to the clone is highly expressed in testis and ovary. Comparison of the deduced amino acid (aa) sequence with those of other S-II molecules shows that (i) the C-terminal zinc finger (Zf) domain is highly conserved, and (ii) the central segment is most similar to that of the rat testis-specific S-II. Further analyses of the hS-II-T1 aa sequence indicate that its N-terminal sequence exhibits similarity to eubacterial sigma 54. The significance of tissue-specific S-II molecules for the regulation of transcription elongation is discussed.
Amino Acid Sequence↗
The sequence of a Xenopus laevis TFIID subunit reveals remarkable conservation among vertebrates.
A cDNA clone encoding a Xenopus laevis (Xl) homologue of human transcription factor IID (TFIID) subunit p80 was isolated and sequenced. The deduced 618-amino-acid (aa) sequence was compared to the homologous from human, mouse, rat and Drosophila melanogaster (Dm). A highly conserved region exists in the central region among these species. In contrast, the C-terminal region has significant homology among vertebrates, whereas the corresponding region of the Dm homologue shows poor homology.
Amino Acid Sequence↗
Evolutionary conservation of human TATA-binding-polypeptide-associated factors TAFII31 and TAFII80 and interactions of TAFII80 with other TAFs and with general transcription factors.
Human transcription initiation factor TFIID is composed of the TATA-binding polypeptide (TBP) and at least 13 TBP-associated factors (TAFs) that collectively or individually are involved in activator-dependent transcription. To investigate protein-protein interactions involved in TFIID assembly and in TAF-mediated activator functions, we have cloned and expressed cDNAs encoding human TAFII80 and TAFII31. Coimmunoprecipitation assays showed that TAFII80 interacted with TAFII250, TAFII31, TAFII20, and TBP, but not with TAFII55. Similar assays showed that TAFII80 interacted with TFIIE alpha and with TFIIF alpha (RAP74) but not with TFIIB, TFIIE beta, or TFIIF beta (RAP30). Further studies with TAFII80 mutations revealed three distinct interaction domains which fall within regions conserved in human TAFII80, Drosophila TAFII60, and yeast TAFII60. The N terminus of TAFII80 (residues 1-100) interacts with both TAFII31 and TAFII20, while two C-terminal regions are involved, respectively, in interactions with TAFII250 and TFIIF alpha (RAP74) (residues 203-276) and with TBP and TFIIE alpha (residues 377-505). The interactions between TAFII80 and general factors TFIIE alpha and TFIIF alpha (RAP74) could be important for recruitment of GTFs during activator-dependent transcription. Because TAFs 80, 31, and 20 show sequence similarities to histones H4, H3, and H2B, as well as some parallel interactions, this subset of TAFs may form a related core structure within TFIID.
Amino Acid Sequence↗
Rapid preparation of plasmid templates suitable for a DNA sequencer without RNase treatment.
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Plasmids↗
Isolation of a cDNA encoding a mouse TFIID subunit containing histone H4 homology.
A cDNA encoding a mouse transcription factor IID (TFIID) subunit, containing histone H4 homology, was cloned and sequenced. The predicted 678-amino-acid (aa) sequence of this molecule showed 97 and 41% identity to the human and Drosophila melanogaster homologues, respectively. Four putative direct repeats were found in the most highly conserved region in the central part of this protein.
Amino Acid Sequence↗
Three distinct regions in a rat TFIID subunit containing histone H4 homology.
A cDNA encoding a rat transcription factor IID (TFIID) subunit (p80), with histone H4 homology, was isolated and sequenced. The deduced amino acid (aa) sequence predicts a 678-aa protein with 97% identity to the human and 42% to the Drosophila melanogaster (Dm) homologues. Homologies between three species indicate the presence of three distinct regions.
Amino Acid Sequence↗
Molecular cloning of cDNA encoding the small subunit of Drosophila transcription initiation factor TFIIF.
Transcription initiation factor TFIIF is a tetramer consisting of two large subunits (TFIIF alpha or RAP74) and two small subunits (TFIIF beta or RAP30). We report here the molecular cloning of a Drosophila cDNA encoding TFIIF beta. The cDNA clone contains an open-reading frame encoding a 277 amino acid polypeptide having a calculated molecular mass of 32,107 Da. Comparison of the deduced amino acid sequence with the corresponding sequences from vertebrates showed only 50% identity, with four insertion/deletion points. For transcription activity in a TFIIF-depleted Drosophila nuclear extract, both TFIIF alpha and TFIIF beta are essential. Moreover, Drosophila TFIIF beta interacts with both Drosophila and human TFIIF alpha in vitro. Thus we conclude that isolated cDNA encodes bona fide TFIIF beta. The structural domains of TFIIF beta and its sequence similarity to bacterial delta factors are discussed.
Amino Acid Sequence↗
c-Myb repression of c-erbB-2 transcription by direct binding to the c-erbB-2 promoter.
The c-myb proto-oncogene product (c-Myb) is a transcriptional activator that can bind to the specific DNA sequences. Although c-Myb also represses an artificial promoter containing the Myb binding sites, natural target genes transcriptionally repressed by c-Myb have not been identified. We have found that the human c-erbB-2 promoter activity is repressed by c-Myb or B-Myb in a chloramphenicol acetyltransferase co-transfection assay. Domain analyses of c-Myb suggested that Myb represses the c-erbB-2 promoter activity by competing with positive regulators of the c-erbB-2 promoter. In in vitro transcription assays, Myb proteins containing only the DNA binding domain could repress c-erbB-2 promoter activity. Two Myb binding sites in the c-erbB-2 promoter were critical for transcriptional repression by c-Myb. One of the two Myb binding sites overlaps the TATA box, and DNase I footprint analyses indicated that c-Myb can compete with TFIID. These results suggest that Myb-induced trans-repression of the c-erbB-2 promoter partly involves competition between Myb and TFIID.
Base Sequence↗
Cooperatively between an upstream TATA-like sequence and a CAA repeated element mediates E1A-dependent negative repression of the H-2Kb class I gene.
In primary rodent cells transformed by the E1A region of the highly oncogenic adenovirus type 12, repression of transcription mediated by the far upstream TATA-like element was observed only in conjunction with either possible juxtaposition of a CAA repeated element in the presence of E1A and was dependent upon the relative arrangement of both the TATA-like and CAA repeated motifs in both homologous and heterologous promoter constructs. A gel shift competition study demonstrated that the TATA-binding protein (TBP) or a TBP-like protein can bind to both the upstream TATA-like sequence and the regular TATA box on the H-2Kb basal promoter. Moreover, employing immunoselection and cyclic amplification and selection of targets (CASTing) methods with nuclear extracts derived from Ad12-E1A transformants, we have identified a high affinity binding site in the H-2Kb class I promoter for E1A-associated DNA-binding proteins. The sequences of the binding sites were identified and were found to contain both the upstream TATA-like motif and the CAA repeated motifs. Our results suggest that the TATA-like sequence in the far upstream region of the H-2Kb gene is one of the elements that is required for Ad12-E1A-mediated negative repression.
Adenovirus E1A Proteins↗
Analysis of the role of TFIIE in basal transcription and TFIIH-mediated carboxy-terminal domain phosphorylation through structure-function studies of TFIIE-alpha.
The general transcription factor TFIIE recruits TFIIH at a late stage of transcription initiation complex formation and markedly stimulates TFIIH-dependent phosphorylation of the carboxy-terminal domain (CTD) of RNA polymerase II. To study this function of TFIIE in more detail, systematic deletion mutations were introduced into the large subunit of TFIIE (TFIIE-alpha) and were analyzed with regard to their effects on TFIIH-dependent CTD phosphorylation, TFIIE-dependent basal and enhancer-dependent transcription, and interactions of TFIIE-alpha with both TFIIE-beta and TFIIH. The amino (N)-terminal half of TFIIE-alpha, which possesses several putative structural motifs, was sufficient for the phosphorylation and transcription activities and for TFIIE-beta interactions, whereas a site effecting both strong interactions with TFIIH and large stimulatory effects on transcription and CTD phosphorylation was localized to an acidic region near the carboxy (C) terminus. The fact that these activities appear to be tightly linked supports the idea that TFIIE interacts physically and functionally with TFIIH and that CTD phosphorylation is essential for transcription under normal conditions. The present results suggest that TFIIE, via its effect on TFIIH, may act as a checkpoint for formation of a preinitiation complex.
Base Sequence↗
Independent control of transcription initiations from two sites by an initiator-like element and TATA box in the human c-erbB-2 promoter.
Transcription of the human c-erbB-2-proto-oncogene starts mainly at two sites, nucleotide positions +1 and -69. The present studies have identified an initiator-like element that specifies the position of transcription initiation at position -69. This initiator-like element contains six GGA repeats and is located just downstream from the transcription start site between positions -68 and -45. In addition, both in vitro and in vivo studies indicated that transcription initiation at position +1 is specified by a TATA box 25 bp upstream from the transcription startpoint. Thus, initiation at two sites in the c-erbB-2 promoter is controlled independently by the initiator-like element and the TATA box.
Base Sequence↗
Effects of activation-defective TBP mutations on transcription initiation in yeast.
Transcription initiation by RNA polymerase II is effected by an ordered series of general factor interactions with core promoter elements (leading to basal activity) and further regulated by gene-specific factors acting from distal elements. Both the general factor TFIID (refs 2,3), including the constituent TBP (TATA-binding polypeptide) and associated factors, and the interacting factor TFIIB (refs 9-11) have been implicated as targets for various activators. Towards an understanding of the basis for activator function, including the multiplicity of TBP interactions, we have now identified mutations in yeast TBP that selectively block activator (GAL4-VP16)-dependent but not basal transcription. We further show an effect of GAL4-VP16 on TFIIB recruitment to early preinitiation complexes, and that recruitment is disrupted by TBP mutations that impair its interactions with VP16 (L114K), TFIIB (L189K) or an unidentified component (K211L). Thus, GAL4-VP16 function seems to involve both direct interactions with TBP and a corresponding induction (or stabilization) of an activation-specific TBP-TFIIB-promoter complex.
Arabidopsis↗
Interaction between the N-terminal domain of the 230-kDa subunit and the TATA box-binding subunit of TFIID negatively regulates TATA-box binding.
Transcription initiation factor TFIID plays a central role in transcriptional regulation. Drosophila TFIID is a multimeric protein consisting of the TATA box-binding polypeptide (TBP) and a number of tightly associated polypeptides. Previously, the largest subunit of TFIID (p230) was cloned and demonstrated to inhibit the TATA-box binding of TBP in the absence of other subunits. Here we demonstrate that p230 contains at least two sites of interaction with TBP and that the N-terminal site mediates both strong physical interactions with TBP and inhibition of the TBP function. A detailed mutagenesis study shows that the inhibitory domain is indistinguishable from the strong TBP-binding domain, thus indicating that interaction of the p230 N-terminal region with TBP may directly control TATA-box binding.
Amino Acid Sequence↗
Molecular cloning of Drosophila TFIID subunits.
Transcription initiation factor TFIID is a multisubunit complex containing a TATA-box-binding factor (TFIID tau/TBP) and associated polypeptide factors (TAFs) with sizes ranging from M(r) approximately 20,000 to > 200,000. As a result of direct promoter interactions, TFIID nucleates the assembly of RNA polymerase II and other initiation factors into a functional preinitiation complex. Although the native TFIID complex mediates both basal and activator-dependent transcription in reconstituted systems, TBP itself is competent for only basal transcription. Thus, TAFs are essential cofactors for regulated transcription. The complementary DNAs encoding the p230 (M(r) 230,000), p110 and p85 subunits of TFIID have recently been cloned. Here we report the molecular cloning and characterization of the p62, p42, p28 and p22 subunits. These participate in a network of heterogeneous protein-protein interactions within TFIID. Sequence similarities between p62/p42 and the histones H4/H3, respectively, suggest that these subunits have a functional relationship with chromatin.
Amino Acid Sequence↗
Direct mapping of the human TATA box-binding protein (TBP) gene to 6q27 by fluorescence in situ hybridization.
TBP (TATA box-binding protein) participates in the expression of eukaryotic genes transcribed by RNA polymerases I, II, and III. Molecular cloning of human TBP revealed that the N-terminal region contains a polymorphic (CAG)n repeat. We report here the direct localization of human TBP gene to chromosome 6q2705-->qter region by fluorescence in situ hybridization, using the cDNA clone with or without the (CAG)n repeat as a probe.
Chromosome Mapping↗
Comparison of interface membranes obtained from failed cemented and cementless hip and knee prostheses.
Biochemical and histologic analyses were performed on interface membranes obtained at revision of aseptically loosened hip implants (n = 36) and knee implants (n = 16). Clinical failure occurred sooner in patients with uncemented total hip implants (Group 1) than in patients with cemented implants (Group 2) (p < 0.02). There was no difference in time to revision between the patients with uncemented implants (Group 3) and patients with cemented total knee implants (Group 4). Histologically, more small (< 5 mu) polyethylene particles were found within macrophages and fibroblasts in membranes from Groups 1 and 2. Polyethylene particles from failed total knees (> 10-100 mu) were larger than those from failed total hips. Large polyethylene fragments and foreign-body giant cells were more common in failed knees than failed total hip membranes. Biochemically, proteinase and cytokine activity in the tissue culture supernatant from all groups was higher than in the control tissue (p < 0.01). The activities of stromelysin, prostaglandin E2, interleukin-1 alpha, interleukin-1 beta, and tumor necrosis factor-alpha were higher in Groups 1 and 2 than in Groups 3 and 4 (p < 0.05). These findings support the hypothesis that interface membranes enveloping femoral (hip) and tibial (knee) components of failed total joint implants may promote bone resorption and aseptic loosening. The reason for slower failure of knee implants as compared with hip prostheses may be the lower level of biochemical activity and macrophage density that correlates closely with larger polyethylene particles.
Aged↗