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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regulated binding of TBP to a promoter is a key event in transcriptional regulation. We show here that on glucose depletion, the S. cerevisiae Isw1 chromatin remodeling complex is required for the displacement of TBP from the PHO8 promoter. Displacement of TBP also requires the sequence-specific bHLH-LZ factor Cbf1p that targets Isw1p to the PHO8 UAS. Cbf1p- and Isw1p-dependent displacement of TBP is also observed at the PHO84 promoter, but not at the ADH1 promoter, where loss of TBP is Cbf1p- and Isw1p independent. The results point to a promoter-specific Isw1p-dependent mechanism for targeted regulation of basal transcription by displacement of TBP from a promoter.
Mol Cell 2003 Jun
PMID:Regulated displacement of TBP from the PHO8 promoter in vivo requires Cbf1 and the Isw1 chromatin remodeling complex. 1282 Sep 73

TBP functions in transcription initiation in all eukaryotes and in Archaebacteria. Although the 181-amino acid (aa) carboxyl (C-) terminal core of the protein is highly conserved, TBP proteins from different phyla exhibit diverse sequences in their amino (N-) terminal region. In mice, the TBP N-terminus plays a role in protecting the placenta from maternal rejection; however the presence of similar TBP N-termini in nontherian tetrapods suggests that this domain also has more primitive functions. To gain insights into the pretherian functions of the N-terminus, we investigated its phylogenetic distribution. TBP cDNAs were isolated from representative nontetrapod jawed vertebrates (zebrafish and shark), from more primitive jawless vertebrates (lamprey and hagfish), and from a prevertebrate cephalochordate (amphioxus). Results showed that the tetrapod N-terminus likely arose coincident with the earliest vertebrates. The primary structures of vertebrate N-termini indicates that, historically, this domain has undergone events involving intragenic duplication and modification of short oligopeptide-encoding DNA sequences, which might have provided a mechanism of de novo evolution of this polypeptide.
Mol Biol Evol 2003 Nov
PMID:Early vertebrate evolution of the TATA-binding protein, TBP. 1288 57

In higher eukaryotes, RNA polymerase (pol) III is known to use different transcription factors to recognize three basic types of promoters, but in no case have these transcription factors been completely defined. We show that a highly purified pol III complex combined with the recombinant transcription factors SNAP(c), TBP, Brf2, and Bdp1 directs multiple rounds of transcription initiation and termination from the human U6 promoter. The pol III complex contains traces of CK2, and CK2 associates with the U6 promoter region in vivo. Transcription requires CK2 phosphorylation of the pol III complex. In contrast, CK2 phosphorylation of TBP, Brf2, and Bdp1 combined is inhibitory. The results define a minimum core machinery, the ultimate target of regulatory mechanisms, capable of directing all steps of the transcription process-initiation, elongation, and termination-by a metazoan RNA polymerase, and suggest positive and negative regulatory roles for CK2 in transcription by pol III.
Mol Cell 2003 Sep
PMID:A minimal RNA polymerase III transcription system from human cells reveals positive and negative regulatory roles for CK2. 1452 15

TFIID and SAGA share a common set of TAFs, regulate chromatin, and deliver TBP to promoters. Here we examine their relationship within the context of the Saccharomyces cerevisiae genome-wide regulatory network. We find that while TFIID and SAGA make overlapping contributions to the expression of all genes, TFIID function predominates at approximately 90% and SAGA at approximately 10% of the measurable genome. Strikingly, SAGA-dominated genes are largely stress induced and TAF independent, and are downregulated by the coordinate action of a variety of chromatin, TBP, and RNA polymerase II regulators. In contrast, the TFIID-dominated class is less regulated, but is highly dependent upon TAFs, including those shared between TFIID and SAGA. These two distinct modes of transcription regulation might reflect the need to balance inducible stress responses with the steady output of housekeeping genes.
Mol Cell 2004 Feb 27
PMID:A genome-wide housekeeping role for TFIID and a highly regulated stress-related role for SAGA in Saccharomyces cerevisiae. 1499 26

Polycomb (PcG) complexes maintain the silent state of target genes. The mechanism of silencing is not known but has been inferred to involve chromatin packaging to block the access of transcription factors. We have studied the effect of PcG silencing on the hsp26 heat shock promoter. While silencing does decrease the accessibility of some restriction enzyme sites to some extent, it does not prevent the binding of TBP, RNA polymerase, or the heat shock factor to the hsp26 promoter, as shown by chromatin immunoprecipitation. However, we find that in the repressed state, the RNA polymerase cannot initiate transcription. We conclude that, rather than altering chromatin structure to block accessibility, PcG silencing in this construct targets directly the activity of the transcriptional machinery at the promoter.
Mol Cell 2004 Mar 26
PMID:Polycomb silencing blocks transcription initiation. 1505 81

Doxorubicin (DOX) is a DNA topoisomerase II inhibitor widely used in anticancer treatment, however, it can lead to irreversible cardiac damage with severe debilitation. TBP-binding associated factor 1 (TAF1) is increased in DOX damaged hearts in vivo and in cardiomyocytes in vitro. To identify the functional role for TAF1 in DOX-treated heart we overexpressed wild type and mutant TAF1 in H9c2 cells. Overexpression of wild-type TAF1, but not N-terminal kinase domain mutants, increased tolerance to DOX in confluent cells. DOX treatment can cause prolonged G1 arrest. We found increased cdk2 activity coupled to increased cyclin E protein and decreased p21(waf1Cip1) and p27(Kip1) protein to correlate only with increased DOX tolerance and wild-type TAF1. DOX sensitivity was restored when the cdk2-inhibitor Roscovitine was co-administered with DOX. Overexpression of cdk2-alone increased resistance to DOX. Thus, TAF1 induced DOX tolerance in confluent cells through an increase in cdk2 activity is directed by the TAF1 N-terminal domain. These studies suggest new avenues for myocardial protection against DOX toxicity and suggest a role for cdk2 in chemorefractory cells.
Mol Cell Biochem 2004 Apr
PMID:TBP-associated factor 1 overexpression induces tolerance to Doxorubicin in confluent H9c2 cells by an increase in cdk2 activity and cyclin E expression. 1512 10

Mot1 associates with transcriptionally active promoters, and it directly affects transcriptional activity in a positive or negative manner, depending on the gene. As determined by sequential chromatin immunoprecipitation, Mot1 co-occupies promoters with TBP, but not with TFIIB, TFIIA, or Pol II when cells are grown in normal conditions. This strongly suggests that the Mot1-TBP complex is transcriptionally inactive, and hence is in dynamic equilibrium with transcriptionally active forms of TBP. Surprisingly, in response to heat shock and other forms of environmental stress, Mot1 co-occupies promoters with TFIIB and elongation-competent Pol II, but not with TFIIA. This suggests that functional preinitiation complexes can contain Mot1 instead of TFIIA in vivo. Thus, Mot1-TBP complexes can exist in active and inactive forms that are regulated by environmental stress.
Mol Cell 2004 May 21
PMID:Cellular stress alters the transcriptional properties of promoter-bound Mot1-TBP complexes. 1514 97

The expression of polyglutamine-expanded mutant proteins in Huntington's disease and other neurodegenerative disorders is associated with the formation of intraneural inclusions. These aggregates could potentially cause cellular toxicity by sequestering essential proteins possessing normal polyQ repeats, including the transcription factors TBP and CBP. We show, in vitro and in cells, that monomers or small soluble oligomers of huntingtin exon1 accumulate in the nucleus and inhibit the function of TBP in a polyQ-dependent manner. FRET experiments indicate that these toxic forms are generated through a conformational rearrangement in huntingtin. Interaction of toxic huntingtin with the benign polyQ repeat of TBP structurally destabilizes the transcription factor, independent of the formation of insoluble coaggregates. Hsp70/Hsp40 chaperones interfere with the conformational change in mutant huntingtin and inhibit the deactivation of TBP. These results outline a molecular mechanism of cellular toxicity in polyQ disease and can explain the beneficial effects of molecular chaperones.
Mol Cell 2004 Jul 02
PMID:Cellular toxicity of polyglutamine expansion proteins: mechanism of transcription factor deactivation. 1522 51

HU is an abundant, highly conserved protein associated with the bacterial chromosome. It belongs to a small class of proteins that includes the eukaryotic proteins TBP, SRY, HMG-I and LEF-I, which bind to DNA non-specifically at the minor groove. HU plays important roles as an accessory architectural factor in a variety of bacterial cellular processes such as DNA compaction, replication, transposition, recombination and gene regulation. In an attempt to unravel the role this protein plays in shaping nucleoid structure, we have carried out fluorescence resonance energy transfer measurements of HU-DNA oligonucleotide complexes, both at the ensemble and single-pair levels. Our results provide direct experimental evidence for concerted DNA bending by HU, and the abrogation of this effect at HU to DNA ratios above about one HU dimer per 10-12 bp. These findings support a model in which a number of HU molecules form an ordered helical scaffold with DNA lying in the periphery. The abrogation of these nucleosome-like structures for high HU to DNA ratios suggests a unique role for HU in the dynamic modulation of bacterial nucleoid structure.
J Mol Biol 2004 Aug 06
PMID:Modulation of DNA conformations through the formation of alternative high-order HU-DNA complexes. 1527 33

Significant numerical and spatial changes in 5-HT i.r. cells, CCK i.r. I-cells, glucagon and glicentin i.r. I-cells, somatostatin i.r. D-cells and neurotensin i.r. N-cells occur after a 98% myenteric ablation in the rat. Signal transduction from G-protein-coupled crypt cell receptors (m2, m3; VCAP1 and 2, CAP1; Y2, Y5, Y4) stimulates a cAMP-responsive transcription machinery in which phosphorylation of the cAMP-responsive elements (e.g. CREB) is the first step in initiation of transcription. A DNA pre-initiation complex (PIC), consisting of DNA transcription activators, general activators (TFIID, IIA, IIB, IIF, IIE, II-I and IIH), at least 14 different TAFIIs and CBP/300 coactivators which contain multiple enzymatic activities, associated with the central TBP (TATA-binding protein), which together bind to the RNA-polymerase II holoenzyme disrupts chromatin blockade over the promoter with or without the intervention of activated chromatin remodeling factors. CBP/p300 contains several highly conserved domains e.g., KIX, whose methylation by CARM-1 represses CREB transcription activation, but the bromo-binding domain of CBP increases CREB transcription. A similar positive/negative switch occurs in the regulation of gastrointestinal hormones by transcription factors, from Myc/Max to Mad/Max + corepressor mSin3A, during terminal differentiation of the cell. From these observations we conclude that the primary targets for neural signals are factors of the basal DNA transcriptional apparatus, whose promoter factors then activate chromatin induction, which facilitates transcription positively or negatively.
Int J Mol Med 2004 Oct
PMID:The influence of neural signal transduction on EEC gene expression under consideration of chromatin, following myenteric ablation (review). 1537 74


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