252. Regulated nuclear import of TATA binding protein associated factor 9 (TAF9) in spermatogenesis

2008 ◽  
Vol 20 (9) ◽  
pp. 52 ◽  
Author(s):  
S. B. Prakash ◽  
J. D. Ly-Huynh ◽  
K. L. Loveland ◽  
D. A. Jans
Keyword(s):  
Nuclear Import ◽  
Transcription Initiation ◽  
Binding Protein ◽  
Core Promoter ◽  
Late Phase ◽  
Tata Binding Protein ◽  
Associated Factor ◽  
Immunohistochemistry Staining ◽  
Dependent Transport ◽  
And Function

Spermatogenesis, the differentiation process resulting in the production of haploid germ cells able to fertilise an oocyte, is driven by nuclear transcription factors, and changes in nuclear morphology and function itself. Signal-dependent transport into and out of the nucleus is mediated by members of the importin (IMP) superfamily of transporters, which we have previously shown to change dynamically in expression profile during spermatogenesis. One IMP family member, IMPα2, is expressed during mid to late phase spermatogenesis, implying that it may transport specific cargoes important for these stages, with a potential cargo of significance identified in a yeast 2-hybrid screen being TAF9 (TATA-Binding Protein Associated Factor 9). TAF9 is an integral part of transcription initiation for many genes, such as those with a Downstream Promoter Element in the core promoter and those with activators such as SOX18, p53, HSF1, NF-IL6 or NF-κB. In addition it participates in histone acetylation complexes which have been previously described to be important for the completion of spermatogenesis. Our preliminary data confirm the interaction of IMPα2 and TAF9 using a cotransfection approach. We have also shown that the expression of these proteins in the testis is correlated using both publically available Affymetrix data, and immunohistochemistry staining. TAF9, like IMPα2, is expressed in the nucleus of elongating spermatids of the adult rodent testis. Our data are thus consistent with the idea that specific nuclear import of TAF9 by IMPα2 may be a critical step in the later stages of spermatogenesis.

scholarly journals Mitochondrial ubiquinone–mediated longevity is marked by reduced cytoplasmic mRNA translation

2018 ◽  
Vol 1 (5) ◽  
pp. e201800082 ◽  
Author(s):  
Marte Molenaars ◽  
Georges E Janssens ◽  
Toon Santermans ◽  
Marco Lezzerini ◽  
Rob Jelier ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
Transcription Initiation ◽  
Binding Protein ◽  
Mrna Translation ◽  
Tata Binding Protein ◽  
Early Embryogenesis ◽  
Life Extension ◽  
Initiation Factor ◽  
Associated Factor ◽  
Transcription Initiation Factor

Mutations in the clk-1 gene impair mitochondrial ubiquinone biosynthesis and extend the lifespan in Caenorhabditis elegans. We demonstrate here that this life extension is linked to the repression of cytoplasmic mRNA translation, independent of the alleged nuclear form of CLK-1. Clk-1 mutations inhibit polyribosome formation similarly to daf-2 mutations that dampen insulin signaling. Comparisons of total versus polysomal RNAs in clk-1(qm30) mutants reveal a reduction in the translational efficiencies of mRNAs coding for elements of the translation machinery and an increase in those coding for the oxidative phosphorylation and autophagy pathways. Knocking down the transcription initiation factor TATA-binding protein-associated factor 4, a protein that becomes sequestered in the cytoplasm during early embryogenesis to induce transcriptional silencing, ameliorates the clk-1 inhibition of polyribosome formation. These results underscore a prominent role for the repression of cytoplasmic protein synthesis in eukaryotic lifespan extension and suggest that mutations impairing mitochondrial function are able to exploit this repression similarly to reductions of insulin signaling. Moreover, this report reveals an unexpected role for TATA-binding protein-associated factor 4 as a repressor of polyribosome formation when ubiquinone biosynthesis is compromised.

Mechanism of initiator-mediated transcription: evidence for a functional interaction between the TATA-binding protein and DNA in the absence of a specific recognition sequence

1993 ◽  
Vol 13 (7) ◽  
pp. 3841-3849
Author(s):  
B Zenzie-Gregory ◽  
A Khachi ◽  
I P Garraway ◽  
S T Smale
Keyword(s):  
Transcription Initiation ◽  
Binding Protein ◽  
Tata Binding Protein ◽  
Upstream Region ◽  
Promoter Strength ◽  
Recognition Sequence ◽  
Specific Recognition ◽  
Rate Limiting

Promoters containing Sp1 binding sites and an initiator element but lacking a TATA box direct high levels of accurate transcription initiation by using a mechanism that requires the TATA-binding protein (TBP). We have begun to address the role of TBP during transcription from Sp1-initiator promoters by varying the nucleotide sequence between -14 and -33 relative to the start site. With each of several promoters containing different upstream sequences, we detected accurate transcription both in vitro and in vivo, but the promoter strengths varied widely, particularly with the in vitro assay. The variable promoter activities correlated with, but were not proportional to, the abilities of the upstream sequences to function as TATA boxes, as assessed by multiple criteria. These results confirm that accurate transcription can proceed in the presence of an initiator, regardless of the sequence present in the -30 region. However, the results reveal a role for this upstream region, most consistent with a model in which initiator-mediated transcription requires binding of TBP to the upstream DNA in the absence of a specific recognition sequence. Moreover, in vivo it appears that the promoter strength is modulated less severely by altering the -30 sequence, consistent with a previous suggestion that TBP is not rate limiting in vivo for TATA-less promoters. Taken together, these results suggest that variations in the structure of a core promoter might alter the rate-limiting step for transcription initiation and thereby alter the potential modes of transcriptional regulation, without severely changing the pathway used to assemble a functional preinitiation complex.

scholarly journals Inhibition of TATA Binding Protein Dimerization by RNA Polymerase III Transcription Initiation Factor Brf1

2004 ◽  
Vol 279 (31) ◽  
pp. 32401-32406 ◽  
Author(s):  
Diane E. Alexander ◽  
David J. Kaczorowski ◽  
Amy J. Jackson-Fisher ◽  
Drew M. Lowery ◽  
Sara J. Zanton ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Transcription Initiation ◽  
Binding Protein ◽  
Rna Polymerase Iii ◽  
Tata Binding Protein ◽  
Initiation Factor ◽  
Protein Dimerization ◽  
Polymerase Iii ◽  
Transcription Initiation Factor

scholarly journals Adeno-Associated Virus Major Rep78 Protein Disrupts Binding of TATA-Binding Protein to the p97 Promoter of Human Papillomavirus Type 16

2000 ◽  
Vol 74 (5) ◽  
pp. 2459-2465 ◽  
Author(s):  
Pei-Fen Su ◽  
Shu-Yuan Chiang ◽  
Cheng-Wen Wu ◽  
Felicia Y.-H. Wu
Keyword(s):  
Human Papillomavirus ◽  
Binding Protein ◽  
Core Promoter ◽  
Tata Binding Protein ◽  
Tata Box ◽  
Dependent Manner ◽  
Hpv 16 ◽  
Adeno Associated Virus ◽  
Human Papillomavirus Type 16 ◽  
E6 And E7

ABSTRACT Adeno-associated virus type 2 (AAV) is known to inhibit the promoter activities of several oncogenes and viral genes, including the human papillomavirus type 16 (HPV-16) E6 and E7 transforming genes. However, the target elements of AAV on the long control region (LCR) upstream of E6 and E7 oncogenes are elusive. A chloramphenicol acetyltransferase assay was performed to study the effect of AAV on the transcription activity of the HPV-16 LCR in SiHa (HPV-positive) and C-33A (HPV-negative) cells. The results reveal that (i) AAV inhibited HPV-16 LCR activity in a dose-dependent manner, (ii) AAV-mediated inhibition did not require the HPV gene products, and (iii) the AAV replication gene product Rep78 was involved in the inhibition. Deletion mutation analyses of the HPV-16 LCR showed that regulatory elements outside the core promoter region of the LCR may not be direct targets of AAV-mediated inhibition. Further study with the electrophoretic mobility shift assay demonstrated that Rep78 interfered with the binding of TATA-binding protein (TBP) to the TATA box of the p97 core promoter more significantly than it disrupted the preformed TBP-TATA complex. These data thus suggest that Rep78 may inhibit transcription initiation of the HPV-16 LCR by disrupting the interaction between TBP and the TATA box of the p97 core promoter.

Optimization of Naphthyridones into Selective TATA-Binding Protein Associated Factor 1 (TAF1) Bromodomain Inhibitors

2021 ◽  
Author(s):  
Michael A. Clegg ◽  
Natalie H. Theodoulou ◽  
Paul Bamborough ◽  
Chun-wa Chung ◽  
Peter D. Craggs ◽  
...  
Keyword(s):  
Binding Protein ◽  
Tata Binding Protein ◽  
Associated Factor

scholarly journals Variations in Intracellular Levels of TATA Binding Protein Can Affect Specific Genes by Different Mechanisms

2007 ◽  
Vol 28 (1) ◽  
pp. 83-92 ◽  
Author(s):  
Stephanie D. Bush ◽  
Patricia Richard ◽  
James L. Manley
Keyword(s):  
Binding Protein ◽  
Core Promoter ◽  
Tata Binding Protein ◽  
Tata Box ◽  
Wild Type ◽  
The Core ◽  
Mitotic Delay ◽  
Reduced Activity ◽  
Dt40 Cells ◽  
Repressor Element

ABSTRACT We previously showed that reduced intracellular levels of the TATA binding protein (TBP), brought about by tbp heterozygosity in DT40 cells, resulted in a mitotic delay reflecting reduced expression of the mitotic regulator cdc25B but did not significantly affect overall transcription. Here we extend these findings in several ways. We first provide evidence that the decrease in cdc25B expression reflects reduced activity of the cdc25B core promoter in the heterozygous (TBP-het) cells. Strikingly, mutations in a previously described repressor element that overlaps the TATA box restored promoter activity in TBP-het cells, supporting the idea that the sensitivity of this promoter to TBP levels reflects a competition between TBP and the repressor for DNA binding. To determine whether cells might have mechanisms to compensate for fluctuations in TBP levels, we next examined expression of the two known vertebrate TBP homologues, TLP and TBP2. Significantly, mRNAs encoding both were significantly overexpressed relative to levels observed in wild-type cells. In the case of TLP, this was shown to reflect regulation of the core promoter by both TBP and TLP. Together, our results indicate that variations in TBP levels can affect the transcription of specific promoters in distinct ways, but overall transcription may be buffered by corresponding alterations in the expression of TBP homologues.

scholarly journals Chromatin Is Permissive to TATA-binding Protein (TBP)-mediated Transcription Initiation

2001 ◽  
Vol 276 (16) ◽  
pp. 12781-12784 ◽  
Author(s):  
Eumorphia Remboutsika ◽  
Xavier Jacq ◽  
Làszlò Tora
Keyword(s):  
Transcription Initiation ◽  
Binding Protein ◽  
Tata Binding Protein
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