Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P20226 (TATA-binding protein)
1,297 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Levels of mRNA and protein encoded by the TATA-binding protein (tbp) gene are shown to increase dramatically during late spermatogenesis in rodents, culminating in a highly testis-enriched expression pattern. Whereas adult spleen and liver contained roughly 0.7 and 2.3 molecules of TBP mRNA per haploid genome-equivalent, respectively, adult testis contained 80-200 molecules of TBP mRNA per haploid genome-equivalent. Comparison of nuclear and cytoplasmic levels of TBP mRNA in liver and testis suggested that nuclear events (transcription or processing) contribute roughly 12-fold, and cytoplasmic events (mRNA stability) roughly 6-fold, to testis-specific overaccumulation. Levels of nuclear TBP protein in testis cells were, on average, 8- and 11-fold higher than those in liver and spleen cells, respectively. Overexpression of TBP mRNA in testis began about 20 days after birth and reached a plateau around day 40, corresponding to the developmental emergence of haploid cells. Besides TBP, two other components of the general RNA polymerase II machinery, TFIIB and RNA polymerase II, were also overexpressed in testis. By immunostaining, it was found that TBP and RNA polymerase II were particularly rich in round spermatid nuclei. Our results suggest a molecular explanation for how early spermatids are able to accumulate all of the mRNA necessary for the final week of spermiogenesis.
...
PMID:High accumulation of components of the RNA polymerase II transcription machinery in rodent spermatids. 767 3

The gene encoding the TATA-binding protein, TBP, is highly overexpressed during the haploid stages of spermatogenesis in rodents. RNase protection analyses for mRNAs containing the previously identified first, second, and eighth exons suggested that most TBP mRNAs in testis did not initiate at the first exon used in somatic cells (here designated exon 1C). Using a sensitive ligation-mediated cDNA amplification method, 5' end variants of TBP mRNA were identified, and the corresponding cDNAs were cloned from liver and testis. In liver, a single promoter/first exon is used to generate a steady-state level of roughly five molecules of TBP mRNA per diploid cell equivalent. In testis, we detect modest up-regulation of the somatic promoter and recruitment of at least five other promoters. Three of the alternative promoter/first exons, including 1C and two of the testis-specific promoter/first exons, 1D and 1E, contribute roughly equivalent amounts of mRNA which, in sum, account for greater than 90% of all TBP mRNA in testis. As a result, round spermatids contain an estimated 1000 TBP mRNA molecules per haploid cell. Testis TBP mRNA also exhibits several low abundance 5' end splicing variants; however, all detected TBP mRNA leader sequences splice onto the common exon 2 and are expected to initiate translation at the same site within exon 2. The precise locations of the three major initiation exons are mapped on the gene. The identification of the strong testis-specific promoter/first exons will be important for understanding spermatid-specific tbp gene regulation.
...
PMID:Spermatid-specific overexpression of the TATA-binding protein gene involves recruitment of two potent testis-specific promoters. 903 Jun 7

Early spermatids contain roughly 1000-fold more TATA-binding protein (TBP) mRNA than do somatic cells. The appearance of TBP-overexpressing spermatids in the developing testis is accompanied by a large increase in whole-organ levels of total RNA and of poly(A)+ RNA per cell. Whereas somatic cells initiate transcription of TBP mRNA at a single promoter/first exon (exon 1C), in adult testis, two additional major promoter/first exons (1D and 1E) are used. We have examined the expression of the somatic and testis-specific TBP mRNA isoforms during rodent testis development. In juvenile testes TBP mRNAs containing either exon 1C or exon 1D, but none containing exon 1E, are detected. At 21 days of age, all TBP mRNA isoforms begin to overaccumulate. The onset of TBP mRNA overaccumulation is marked first by an increase in levels of polysomal TBP mRNA, and later by accumulation of mRNP-associated TBP mRNA. In adult testes, only 30% of the total TBP mRNA is engaged by polysomes; the remainder is sequestered as mRNP particles. All of the TBP mRNA isoforms in adults exist both as free mRNP particles and as polysomes; however, the fraction in polysomes varies from 60% (exon 1C) to 10% (exon 1E). This suggests that sequences within the first exons alter the probability that the mRNA will either assemble into polysomes or into translationally inactive mRNP particles.
...
PMID:Developmental testis-specific regulation of mRNA levels and mRNA translational efficiencies for TATA-binding protein mRNA isoforms. 914 90

The general transcription factor IIA (TFIIA) stimulates RNA polymerase II-specific transcription by stabilizing the association of the TATA-binding protein (TBP) with promoter DNA, inhibiting repressors of TBP, and facilitating activator-dependent conformational changes in the preinitiation complex. TFIIA is encoded by two genes (alphabeta and gamma) that are highly conserved between human and yeast. Here, we report the molecular cloning of a novel human gene that shares significant sequence similarity to the evolutionarily conserved amino- and carboxyl-terminal domains of TFIIAalphabeta. The TFIIA-related protein (TFIIAtau) was cloned from a testis-specific cDNA library, and its mRNA is expressed predominantly in testis tissue as determined by expressed sequence tag data base analysis and Northern blotting analysis. The TFIIA complex reconstituted with the testis-specific subunit, TFIIA (tau+gamma), formed the TFIIA-TBP-TATA DNA (T-A) and TFIIA-TFIIB-TBP-TATA DNA (TAB) complexes indistinguishably from TFIIA (alphabeta+gamma). TFIIA (tau+gamma) supported basal and activated transcription for most activators in reactions reconstituted with TFIIA-depleted nuclear extracts. However, TFIIA (tau+gamma) was reduced relative to TFIIA (alphabeta+gamma) for stimulating transcription with at least one activator, suggesting that these two forms of TFIIA have activator specificity. These results suggest that TFIIAtau may be important for testis-specific transcription regulation.
...
PMID:A testis-specific transcription factor IIA (TFIIAtau) stimulates TATA-binding protein-DNA binding and transcription activation. 1061 94

The assembly and stability of the RNA polymerase II transcription preinitiation complex on a eukaryotic core promoter involves the effects of TFIIA on the interaction between TATA-binding protein (TBP) and DNA. To extend our understanding of these interactions, we characterized properties of ALF, a germ cell-specific TFIIA-like factor. ALF was able to stabilize the binding of TBP to DNA, but it could not stabilize TBP mutants A184E, N189E, E191R, and R205E nor could it facilitate binding of the TBP-like factor TRF2/TLF to a consensus TATA element. However, phosphorylation of ALF with casein kinase II resulted in the partial restoration of complex formation using mutant TBPs. Studies of ALF-TBP complexes formed on the Adenovirus Major Late (AdML) promoter revealed protection of the TATA box and upstream sequences from -38 to -20 (top strand) and -40 to -22 (bottom strand). The half-life and apparent K(D) of this complex was determined to be 650 min and 4.8 +/- 2.7 nm, respectively. The presence of ALF or TFIIA did not significantly alter the ability of TBP to bind TATA elements from several testis-specific genes. Finally, analysis of the distinct, nonhomologous internal regions of ALF and TFIIAalpha/beta using circular dichroism spectroscopy provided the first evidence to suggest that these domains are unordered, a result consistent with other genetic and biochemical properties. Overall, the results show that while the sequence and regulation of the ALF gene are distinct from its somatic cell counterpart TFIIAalpha/beta, the TFIIAgamma-dependent interactions of these factors with TBP are nearly indistinguishable in vitro. Thus, a role for ALF in the assembly and stabilization of initiation complexes in germ cells is likely to be similar or identical to the role of TFIIA in somatic cells.
...
PMID:The germ cell-specific transcription factor ALF. Structural properties and stabilization of the TATA-binding protein (TBP)-DNA complex. 1210 78

The gene encoding TATA-binding protein-related factor 2 (TRF2/TLF/TLP/TRP), essential for the progress of spermiogenesis, is abundantly expressed in mammalian testis. A sequence database search revealed that mouse TRF2 is encoded by two mRNAs containing the same protein-coding region and different 5'-untranslated regions. Northern blot analysis using DNA probes specific for the 5'-untranslated regions demonstrated that these two mRNAs are distinguished from each other by the expression patterns: ubiquitous and testis-specific expression. The ubiquitously expressed form of TRF2 mRNA was present at a very low level throughout testicular development, whereas expression of the testis-specific form was first detectable in the 14-day-old testis, and the mRNA level abundantly increased at the later stages of testicular development. Western blot analysis indicated that the TRF2 level increases during testicular development, which is consistent with the expression pattern of the testicular form of TRF2 mRNA. Thus, the presence of the testis-specific form of TRF2 mRNA may account for overexpression of the TRF2 gene in the testis.
...
PMID:Expression of a testis-specific form of TBP-related factor 2 (TRF2) mRNA during mouse spermatogenesis. 1496 55

Male germ-cell differentiation requires spermatogenic stage- and cell-specific gene expression that is achieved by unique chromatin remodeling, transcriptional control and the expression of testis-specific genes or isoforms. Recent findings have shown that the testis has specialized transcription complexes that coordinate the differentiation program of spermatogenesis. There are male germ cell-specific differences in the components of the general transcription machinery. These include upregulated expression of the TATA-binding protein (TBP) family and its associated cofactors. Importantly, a member of the TBP family, TBP-like factor (TLF), has a distribution pattern that is dependent on the spermatogenic cycle and is essential for spermatogenesis. Interestingly TBP-associated factor (TAF7), a factor of the transcription factor (TF)IID complex, is exchanged at a critical stage in germ cell development for the testis-specific paralogue TAF7L. A compelling amount of data has established that cAMP-response-element modulator (CREM), a transcription factor responsive to the cAMP signal transduction pathway, drives expression of key testis-specific genes. In this review we summarize recent advances in the transcription machinery that is testis-specific, gene-selective and necessary for the process of spermatogenesis.
...
PMID:Testis-specific transcription mechanisms promoting male germ-cell differentiation. 1523 59

Specialized transcription complexes that coordinate the differentiation programme of spermatogenesis have been found in germ cells, which display specific differences in the components of the general transcription machinery. The TATA-binding protein family and its associated cofactors, for example, show upregulated expression in testis. In this physiological context, transcriptional control mediated by the activator cAMP response element modulator (CREM) represents an established paradigm. Somatic cell activation by CREM requires its phosphorylation at a unique regulatory site (Ser117) and subsequent interaction with the ubiquitous coactivator CREB-binding protein. In testis, CREM transcriptional activity is controlled through interaction with a tissue-specific partner, activator of CREM in the testis (ACT), which confers a powerful, phosphorylation-independent activation capacity. The function of ACT was found to be regulated by the testis-specific kinesin KIF17b. Here we discuss some aspects of the testis-specific transcription machinery, whose function is essential for the process of spermatogenesis.
...
PMID:Specialized rules of gene transcription in male germ cells: the CREM paradigm. 1559 50

In Drosophila, testis-specific TBP-associated factors (tTAFs) predominantly localize to spermatocyte nucleoli and regulate the transcription of genes necessary for spermatocyte entry into meiosis. tTAFs are paralogs of generally expressed TAF subunits of transcription factor IID (TFIID). Our recent observation that the generally expressed TAF1 isoform TAF1-2 is greatly enriched in testes prompted us to explore the functional relationship between general TAFs and tTAFs during spermatogenesis. Analysis by immunofluorescence microscopy revealed that among the general TFIID subunits examined (TATA-box binding protein [TBP], TAF1, TAF4, TAF5, and TAF9), only TAF1 colocalized with the tTAF Mia in spermatocyte nucleoli. Nucleolar localization of TAF1, but not Mia, was disrupted in tTAF mutant flies, and TAF1 dissociated from DNA prior to Mia as spermatocytes entered meiosis. Taken together, our results suggest stepwise assembly of a testis-specific TFIID complex (tTFIID) whereby a TAF1 isoform, presumably TAF1-2, is recruited to a core subassembly of tTAFs in spermatocyte nucleoli.
...
PMID:Nucleolar colocalization of TAF1 and testis-specific TAFs during Drosophila spermatogenesis. 1782 58

A key step in many chromatin-related processes is the recognition of histone post-translational modifications by effector modules such as bromodomains and chromo-like domains of the Royal family. Whereas effector-mediated recognition of single post-translational modifications is well characterized, how the cell achieves combinatorial readout of histones bearing multiple modifications is poorly understood. One mechanism involves multivalent binding by linked effector modules. For example, the tandem bromodomains of human TATA-binding protein-associated factor-1 (TAF1) bind better to a diacetylated histone H4 tail than to monoacetylated tails, a cooperative effect attributed to each bromodomain engaging one acetyl-lysine mark. Here we report a distinct mechanism of combinatorial readout for the mouse TAF1 homologue Brdt, a testis-specific member of the BET protein family. Brdt associates with hyperacetylated histone H4 (ref. 7) and is implicated in the marked chromatin remodelling that follows histone hyperacetylation during spermiogenesis, the stage of spermatogenesis in which post-meiotic germ cells mature into fully differentiated sperm. Notably, we find that a single bromodomain (BD1) of Brdt is responsible for selectively recognizing histone H4 tails bearing two or more acetylation marks. The crystal structure of BD1 bound to a diacetylated H4 tail shows how two acetyl-lysine residues cooperate to interact with one binding pocket. Structure-based mutagenesis that reduces the selectivity of BD1 towards diacetylated tails destabilizes the association of Brdt with acetylated chromatin in vivo. Structural analysis suggests that other chromatin-associated proteins may be capable of a similar mode of ligand recognition, including yeast Bdf1, human TAF1 and human CBP/p300 (also known as CREBBP and EP300, respectively). Our findings describe a new mechanism for the combinatorial readout of histone modifications in which a single effector module engages two marks on a histone tail as a composite binding epitope.
...
PMID:Cooperative binding of two acetylation marks on a histone tail by a single bromodomain. 1979 95


1 2 Next >>

---