scholarly journals Regulation of TATA-Binding Protein Binding by the SAGA Complex and the Nhp6 High-Mobility Group Protein

2003 ◽  
Vol 23 (6) ◽  
pp. 1910-1921 ◽  
Author(s):  
Yaxin Yu ◽  
Peter Eriksson ◽  
Leena T. Bhoite ◽  
David J. Stillman
Keyword(s):  
Transcription Factor ◽  
Synthetic Lethality ◽  
Binding Protein ◽  
High Mobility ◽  
Tata Binding Protein ◽  
High Mobility Group ◽  
Saga Complex ◽  
High Mobility Group Protein ◽  
Group Protein

ABSTRACT Transcriptional activation of the yeast HO gene involves the sequential action of DNA-binding and chromatin-modifying factors. Here we examine the role of the SAGA complex and the Nhp6 architectural transcription factor in HO regulation. Our data suggest that these factors regulate binding of the TATA-binding protein (TBP) to the promoter. A gcn5 mutation, eliminating the histone acetyltransferase present in SAGA, reduces the transcription of HO, but expression is restored in a gcn5 spt3 double mutant. We conclude that the major role of Gcn5 in HO activation is to overcome repression by Spt3. Spt3 is also part of SAGA, and thus two proteins in the same regulatory complex can have opposing roles in transcriptional regulation. Chromatin immunoprecipitation experiments show that TBP binding to HO is very weak in wild-type cells but markedly increased in an spt3 mutant, indicating that Spt3 reduces HO expression by inhibiting TBP binding. In contrast, it has been shown previously that Spt3 stimulates TBP binding to the GAL1 promoter as well as GAL1 expression, and thus, Spt3 regulates these promoters differently. We also find genetic interactions between TBP and either Gcn5 or the high-mobility-group protein Nhp6, including multicopy suppression and synthetic lethality. These results suggest that, while Spt3 acts to inhibit TBP interaction with the HO promoter, Gcn5 and Nhp6 act to promote TBP binding. The result of these interactions is to limit TBP binding and HO expression to a short period within the cell cycle. Furthermore, the synthetic lethality resulting from combining a gcn5 mutation with specific TBP point mutations can be suppressed by the overexpression of transcription factor IIA (TFIIA), suggesting that histone acetylation by Gcn5 can stimulate transcription by promoting the formation of a TBP/TFIIA complex.

scholarly journals TATA-Binding Protein Mutants That Are Lethal in the Absence of the Nhp6 High-Mobility-Group Protein

2004 ◽  
Vol 24 (14) ◽  
pp. 6419-6429 ◽  
Author(s):  
Peter Eriksson ◽  
Debabrata Biswas ◽  
Yaxin Yu ◽  
James M. Stewart ◽  
David J. Stillman
Keyword(s):  
Rna Polymerase Ii ◽  
Transcriptional Activation ◽  
Synthetic Lethality ◽  
Binding Protein ◽  
High Mobility ◽  
Tata Binding Protein ◽  
High Mobility Group ◽  
Multicopy Plasmid ◽  
Pol Ii ◽  
Pol Iii

ABSTRACT The Saccharomyces cerevisiae Nhp6 protein is related to the high-mobility-group B family of architectural DNA-binding proteins that bind DNA nonspecifically but bend DNA sharply. Nhp6 is involved in transcriptional activation by both RNA polymerase II (Pol II) and Pol III. Our previous genetic studies have implicated Nhp6 in facilitating TATA-binding protein (TBP) binding to some Pol II promoters in vivo, and we have used a novel genetic screen to isolate 32 new mutations in TBP that are viable in wild-type cells but lethal in the absence of Nhp6. The TBP mutations that are lethal in the absence of Nhp6 cluster in three regions: on the upper surface of TBP that may have a regulatory role, near residues that contact Spt3, or near residues known to contact either TFIIA or Brf1 (in TFIIIB). The latter set of mutations suggests that Nhp6 becomes essential when a TBP mutant compromises its ability to interact with either TFIIA or Brf1. Importantly, the synthetic lethality for some of the TBP mutations is suppressed by a multicopy plasmid with SNR6 or by an spt3 mutation. It has been previously shown that nhp6ab mutants are defective in expressing SNR6, a Pol III-transcribed gene encoding the U6 splicing RNA. Chromatin immunoprecipitation experiments show that TBP binding to SNR6 is reduced in an nhp6ab mutant. Nhp6 interacts with Spt16/Pob3, the yeast equivalent of the FACT elongation complex, consistent with nhp6ab cells being extremely sensitive to 6-azauracil (6-AU). However, this 6-AU sensitivity can be suppressed by multicopy SNR6 or BRF1. Additionally, strains with SNR6 promoter mutations are sensitive to 6-AU, suggesting that decreased SNR6 RNA levels contribute to 6-AU sensitivity. These results challenge the widely held belief that 6-AU sensitivity results from a defect in transcriptional elongation.

A crucial role of a high mobility group protein HMGA2 in cardiogenesis

2008 ◽  
Vol 10 (5) ◽  
pp. 567-574 ◽  
Author(s):  
Koshiro Monzen ◽  
Yuzuru Ito ◽  
Atsuhiko T. Naito ◽  
Hiroki Kasai ◽  
Yukio Hiroi ◽  
...  
Keyword(s):  
Crucial Role ◽  
High Mobility ◽  
High Mobility Group ◽  
High Mobility Group Protein ◽  
Group Protein

scholarly journals Functional roles of the transcription factor Oct-2A and the high mobility group protein I/Y in HLA-DRA gene expression.

1995 ◽  
Vol 182 (2) ◽  
pp. 487-500 ◽  
Author(s):  
S A Abdulkadir ◽  
S Krishna ◽  
D Thanos ◽  
T Maniatis ◽  
J L Strominger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
B Cells ◽  
B Cell ◽  
Cell Lines ◽  
High Mobility ◽  
High Mobility Group ◽  
High Mobility Group Protein ◽  
Ifn Gamma ◽  
Group Protein

The class II major histocompatibility complex gene HLA-DRA is expressed in B cells, activated T lymphocytes, and in antigen-presenting cells. In addition, HLA-DRA gene expression is inducible in a variety of cell types by interferon-gamma (IFN-gamma). Here we show that the lymphoid-specific transcription factor Oct-2A plays a critical role in HLA-DRA gene expression in class II-positive B cell lines, and that the high mobility group protein (HMG) I/Y binds to multiple sites within the DRA promoter, including the Oct-2A binding site. Coexpression of HMG I/Y and Oct-2 in cell lines lacking Oct-2 results in high levels of HLA-DRA gene expression, and in vitro DNA-binding studies reveal that HMG I/Y stimulates Oct-2A binding to the HLA-DRA promoter. Thus, Oct-2A and HMG I/Y may synergize to activate HLA-DRA expression in B cells. By contrast, Oct-2A is not involved in the IFN-gamma induction of the HLA-DRA gene in HeLa cells, but antisense HMG I/Y dramatically decreases the level of induction. We conclude that distinct sets of transcription factors are involved in the two modes of HLA-DRA expression, and that HMG I/Y may be important for B cell-specific expression, and is essential for IFN-gamma induction.

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