The yeast heat shock transcription factor contains a transcriptional activation domain whose activity is repressed under nonshock conditions

Cell ◽  
1990 ◽  
Vol 62 (4) ◽  
pp. 807-817 ◽  
Author(s):  
Jorge Nieto-Sotelo ◽  
Greg Wiederrecht ◽  
Akihiko Okuda ◽  
Carl S. Parker
Keyword(s):  
Transcription Factor ◽  
Heat Shock ◽  
Transcriptional Activation ◽  
Heat Shock Transcription Factor ◽  
Activation Domain ◽  
Transcriptional Activation Domain

scholarly journals Temperature-dependent regulation of a heterologous transcriptional activation domain fused to yeast heat shock transcription factor.

1992 ◽  
Vol 12 (3) ◽  
pp. 1021-1030 ◽  
Author(s):  
J J Bonner ◽  
S Heyward ◽  
D L Fackenthal
Keyword(s):  
Transcription Factor ◽  
Heat Shock ◽  
Dna Binding ◽  
Transcriptional Activation ◽  
Heat Shock Transcription Factor ◽  
Temperature Dependent ◽  
Activation Domain ◽  
Yeast Saccharomyces Cerevisiae ◽  
Transcriptional Activation Domain ◽  
Vp16 Fusion

The heat shock transcription factor (HSF) of the yeast Saccharomyces cerevisiae is posttranslationally modified. At low growth temperatures, it activates transcription of heat shock genes only poorly; after shift to high temperatures, it activates transcription readily. In an effort to elucidate the mechanism of this regulation, we constructed a series of HSF-VP16 fusions that join the HSF DNA-binding domain to the strong transcriptional activation domain from the VP16 gene of herpes simplex virus. Replacement of the endogenous C-terminal transcriptional activation domain with that of VP16 generates an HSF derivative that exhibits behavior reminiscent of HSF itself: low transcriptional activation activity at normal growth temperature and high activity after heat shock. HSF can thus restrain the activity of the heterologous VP16 transcriptional activation domain. To determine what is required for repression of activity at low temperature, we deleted portions of HSF from this HSF-VP16 fusion to map the regulatory domain. We also isolated point mutations that convert the HSF-VP16 fusion into a constitutive transcriptional activator. We conclude that the central, evolutionarily conserved domain of HSF, encompassing the DNA-binding and multimerization domains, contains a major determinant of temperature-dependent regulation.

Temperature-dependent regulation of a heterologous transcriptional activation domain fused to yeast heat shock transcription factor

1992 ◽  
Vol 12 (3) ◽  
pp. 1021-1030
Author(s):  
J J Bonner ◽  
S Heyward ◽  
D L Fackenthal
Keyword(s):  
Transcription Factor ◽  
Heat Shock ◽  
Dna Binding ◽  
Transcriptional Activation ◽  
Heat Shock Transcription Factor ◽  
Temperature Dependent ◽  
Activation Domain ◽  
Yeast Saccharomyces Cerevisiae ◽  
Transcriptional Activation Domain ◽  
Vp16 Fusion

The heat shock transcription factor (HSF) of the yeast Saccharomyces cerevisiae is posttranslationally modified. At low growth temperatures, it activates transcription of heat shock genes only poorly; after shift to high temperatures, it activates transcription readily. In an effort to elucidate the mechanism of this regulation, we constructed a series of HSF-VP16 fusions that join the HSF DNA-binding domain to the strong transcriptional activation domain from the VP16 gene of herpes simplex virus. Replacement of the endogenous C-terminal transcriptional activation domain with that of VP16 generates an HSF derivative that exhibits behavior reminiscent of HSF itself: low transcriptional activation activity at normal growth temperature and high activity after heat shock. HSF can thus restrain the activity of the heterologous VP16 transcriptional activation domain. To determine what is required for repression of activity at low temperature, we deleted portions of HSF from this HSF-VP16 fusion to map the regulatory domain. We also isolated point mutations that convert the HSF-VP16 fusion into a constitutive transcriptional activator. We conclude that the central, evolutionarily conserved domain of HSF, encompassing the DNA-binding and multimerization domains, contains a major determinant of temperature-dependent regulation.

scholarly journals A trans-Activation Domain in Yeast Heat Shock Transcription Factor Is Essential for Cell Cycle Progression during Stress

1999 ◽  
Vol 19 (1) ◽  
pp. 402-411 ◽  
Author(s):  
Kevin A. Morano ◽  
Nicholas Santoro ◽  
Keith A. Koch ◽  
Dennis J. Thiele
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Heat Shock ◽  
Cell Cycle Arrest ◽  
Transcriptional Activation ◽  
Heat Shock Transcription Factor ◽  
Yeast Cells ◽  
Activation Domain ◽  
Cycle Arrest ◽  
Carboxyl Terminal

ABSTRACT Gene expression in response to heat shock is mediated by the heat shock transcription factor (HSF), which in yeast harbors both amino- and carboxyl-terminal transcriptional activation domains. Yeast cells bearing a truncated form of HSF in which the carboxyl-terminal transcriptional activation domain has been deleted [HSF(1-583)] are temperature sensitive for growth at 37°C, demonstrating a requirement for this domain for sustained viability during thermal stress. Here we demonstrate that HSF(1-583) cells undergo reversible cell cycle arrest at 37°C in the G2/M phase of the cell cycle and exhibit marked reduction in levels of the molecular chaperone Hsp90. As in higher eukaryotes, yeast possesses two nearly identical isoforms of Hsp90: one constitutively expressed and one highly heat inducible. When expressed at physiological levels in HSF(1-583) cells, the inducible Hsp90 isoform encoded by HSP82 more efficiently suppressed the temperature sensitivity of this strain than the constitutively expressed gene HSC82, suggesting that different functional roles may exist for these chaperones. Consistent with a defect in Hsp90 production, HSF(1-583) cells also exhibited hypersensitivity to the Hsp90-binding ansamycin antibiotic geldanamycin. Depletion of Hsp90 from yeast cells wild type for HSF results in cell cycle arrest in both G1/S and G2/M phases, suggesting a complex requirement for chaperone function in mitotic division during stress.

scholarly journals Multiple layers of regulation of human heat shock transcription factor 1.

1995 ◽  
Vol 15 (8) ◽  
pp. 4319-4330 ◽  
Author(s):  
J Zuo ◽  
D Rungger ◽  
R Voellmy
Keyword(s):  
Transcription Factor ◽  
Heat Shock ◽  
Dna Binding ◽  
Cell Activation ◽  
Transcription Activation ◽  
Heat Shock Transcription Factor ◽  
Activation Domain ◽  
Sequence Element ◽  
Transcription Activation Domain ◽  
Transcription Factor 1

Upon heat stress, monomeric human heat shock transcription factor 1 (hHSF1) is converted to a trimer, acquires DNA-binding ability, is transported to the nucleus, and becomes transcriptionally competent. It was not known previously whether these regulatory changes are caused by a single activation event or whether they occur independently from one another, providing a multilayered control that may prevent inadvertant activation of hHSF1. Comparison of wild-type and mutant hHSF1 expressed in Xenopus oocytes and human HeLa cells suggested that retention of hHSF1 in the monomeric form depends on hydrophobic repeats (LZ1 to LZ3) and a carboxy-terminal sequence element in hHSF1 as well as on the presence of a titratable factor in the cell. Oligomerization of hHSF1 appears to induce DNA-binding activity as well as to uncover an amino-terminally located nuclear localization signal. A mechanism distinct from that controlling oligomerization regulates the transcriptional competence of hHSF1. Components of this mechanism were mapped to a region, including LZ2 and nearby sequences downstream from LZ2, that is clearly separated from the carboxy-terminally located transcription activation domain(s). We propose the existence of a fold-back structure that masks the transcription activation domain in the unstressed cell but is opened up by modification of hHSF1 and/or binding of a factor facilitating hHSF1 unfolding in the stressed cell. Activation of hHSF1 appears to involve at least two independently regulated structural transitions.

scholarly journals Structural and functional properties of the N transcriptional activation domain of thyroid transcription factor-1: similarities with the acidic activation domains

1998 ◽  
Vol 329 (2) ◽  
pp. 395-403 ◽  
Author(s):  
Gianluca TELL ◽  
Lorena PERRONE ◽  
Dora FABBRO ◽  
Lucia PELLIZZARI ◽  
Carlo PUCILLO ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcriptional Activation ◽  
Activation Domain ◽  
Activation Domains ◽  
Transcriptional Activation Domain ◽  
Acidic Domain ◽  
Thyroid Transcription Factor 1 ◽  
Thyroid Transcription Factor ◽  
Transcriptional Activation Domains ◽  
Transcription Factor 1

The thyroid transcription factor 1 (TTF-1) is a tissue-specific transcription factor involved in the development of thyroid and lung. TTF-1 contains two transcriptional activation domains (N and C domain). The primary amino acid sequence of the N domain does not show any typical characteristic of known transcriptional activation domains. In aqueous solution the N domain exists in a random-coil conformation. The increase of the milieu hydrophobicity, by the addition of trifluoroethanol, induces a considerable gain of α-helical structure. Acidic transcriptional activation domains are largely unstructured in solution, but, under hydrophobic conditions, folding into α-helices or β-strands can be induced. Therefore our data indicate that the inducibility of α-helix by hydrophobic conditions is a property not restricted to acidic domains. Co-transfections experiments indicate that the acidic domain of herpes simplex virus protein VP16 (VP16) and the TTF-1 N domain are interchangeable and that a chimaeric protein, which combines VP16 linked to the DNA-binding domain of TTF-1, undergoes the same regulatory constraints that operate for the wild-type TTF-1. In addition, we demonstrate that the TTF-1 N domain possesses two typical properties of acidic activation domains: TBP (TATA-binding protein) binding and ability to activate transcription in yeast. Accordingly, the TTF-1 N domain is able to squelch the activity of the p65 acidic domain. Altogether, these structural and functional data suggest that a non-acidic transcriptional activation domain (TTF-1 N domain) activates transcription by using molecular mechanisms similar to those used by acidic domains. TTF-1 N domain and acidic domains define a family of proteins whose common property is to activate transcription through the use of mechanisms largely conserved during evolutionary development.

scholarly journals Heat Shock Element Architecture Is an Important Determinant in the Temperature and Transactivation Domain Requirements for Heat Shock Transcription Factor

1998 ◽  
Vol 18 (11) ◽  
pp. 6340-6352 ◽  
Author(s):  
Nicholas Santoro ◽  
Nina Johansson ◽  
Dennis J. Thiele
Keyword(s):  
Transcription Factor ◽  
Heat Shock ◽  
Transcriptional Activation ◽  
Single Gene ◽  
Limited Proteolysis ◽  
Normal Growth ◽  
Heat Shock Transcription Factor ◽  
Transactivation Domain ◽  
Heat Shock Element

ABSTRACT The baker’s yeast Saccharomyces cerevisiae possesses a single gene encoding heat shock transcription factor (HSF), which is required for the activation of genes that participate in stress protection as well as normal growth and viability. Yeast HSF (yHSF) contains two distinct transcriptional activation regions located at the amino and carboxyl termini. Activation of the yeast metallothionein gene, CUP1, depends on a nonconsensus heat shock element (HSE), occurs at higher temperatures than other heat shock-responsive genes, and is highly dependent on the carboxyl-terminal transactivation domain (CTA) of yHSF. The results described here show that the noncanonical (or gapped) spacing of GAA units in the CUP1HSE (HSE1) functions to limit the magnitude of CUP1transcriptional activation in response to heat and oxidative stress. The spacing in HSE1 modulates the dependence for transcriptional activation by both stresses on the yHSF CTA. Furthermore, a previously uncharacterized HSE in the CUP1 promoter, HSE2, modulates the magnitude of the transcriptional activation of CUP1, via HSE1, in response to stress. In vitro DNase I footprinting experiments suggest that the occupation of HSE2 by yHSF strongly influences the manner in which yHSF occupies HSE1. Limited proteolysis assays show that HSF adopts a distinct protease-sensitive conformation when bound to the CUP1HSE1, providing evidence that the HSE influences DNA-bound HSF conformation. Together, these results suggest that CUP1regulation is distinct from that of other classic heat shock genes through the interaction of yHSF with two nonconsensus HSEs. Consistent with this view, we have identified other gene targets of yHSF containing HSEs with sequence and spacing features similar to those ofCUP1 HSE1 and show a correlation between the spacing of the GAA units and the relative dependence on the yHSF CTA.

scholarly journals Genome-wide Analysis Reveals New Roles for the Activation Domains of the Saccharomyces cerevisiae Heat Shock Transcription Factor (Hsf1) during the Transient Heat Shock Response

2006 ◽  
Vol 281 (43) ◽  
pp. 32909-32921 ◽  
Author(s):  
Dawn L. Eastmond ◽  
Hillary C. M. Nelson
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Transcription Factor ◽  
Heat Shock ◽  
Heat Shock Transcription Factor ◽  
Functional Categories ◽  
Activation Domain ◽  
Activation Domains ◽  
Genome Wide ◽  
Wide Range ◽  
Induced Genes

In response to elevated temperatures, cells from many organisms rapidly transcribe a number of mRNAs. In Saccharomyces cerevisiae, this protective response involves two regulatory systems: the heat shock transcription factor (Hsf1) and the Msn2 and Msn4 (Msn2/4) transcription factors. Both systems modulate the induction of specific heat shock genes. However, the contribution of Hsf1, independent of Msn2/4, is only beginning to emerge. To address this question, we constructed an msn2/4 double mutant and used microarrays to elucidate the genome-wide expression program of Hsf1. The data showed that 7.6% of the genome was heat-induced. The up-regulated genes belong to a wide range of functional categories, with a significant increase in the chaperone and metabolism genes. We then focused on the contribution of the activation domains of Hsf1 to the expression profile and extended our analysis to include msn2/4Δ strains deleted for the N-terminal or C-terminal activation domain of Hsf1. Cluster analysis of the heat-induced genes revealed activation domain-specific patterns of expression, with each cluster also showing distinct preferences for functional categories. Computational analysis of the promoters of the induced genes affected by the loss of an activation domain showed a distinct preference for positioning and topology of the Hsf1 binding site. This study provides insight into the important role that both activation domains play for the Hsf1 regulatory system to rapidly and effectively transcribe its regulon in response to heat shock.

scholarly journals YY1 controls Eμ-3′RR DNA loop formation and immunoglobulin heavy chain class switch recombination

2016 ◽  
Vol 1 (1) ◽  
pp. 15-20 ◽  
Author(s):  
Parul Mehra ◽  
Tatiana Gerasimova ◽  
Arindam Basu ◽  
Vibha Jha ◽  
Anupam Banerjee ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcriptional Activation ◽  
Loop Formation ◽  
Long Distance ◽  
Activation Domain ◽  
Transcriptional Activation Domain ◽  
Class Switch ◽  
Dna Loop ◽  
Key Points ◽  
Transcription Factor Yy1

Key Points Transcription factor YY1 regulates the IgH Eμ-3′RR long-distance DNA loop without the YY1 transcriptional activation domain. YY1 constructs that rescue the Eμ-3′RR DNA loop also restore CSR strongly arguing for the necessity of this long-distance DNA loop for CSR.

scholarly journals OCA-B is a functional analog of VP16 but targets a separate surface of the Oct-1 POU domain.

1997 ◽  
Vol 17 (12) ◽  
pp. 7295-7305 ◽  
Author(s):  
R Babb ◽  
M A Cleary ◽  
W Herr
Keyword(s):  
Transcription Factor ◽  
Herpes Simplex ◽  
Transcriptional Activation ◽  
Activation Domain ◽  
Transcriptional Activation Domain ◽  
Pou Domain ◽  
Functional Analog ◽  
Simplex Virus ◽  
Structural Versatility ◽  
Binding Structure

OCA-B is a B-cell-specific coregulator of the broadly expressed POU domain transcription factor Oct-1. OCA-B associates with the Oct-1 POU domain, a bipartite DNA-binding structure containing a POU-specific (POU[S]) domain joined by a flexible linker to a POU homeodomain (POU[H]). Here, we show that OCA-B alters the activity of Oct-1 in two ways. It provides a transcriptional activation domain which, unlike Oct-1, activates an mRNA-type promoter effectively, and it stabilizes Oct-1 on the Oct-1-responsive octamer sequence ATGCAAAT. These properties of OCA-B parallel those displayed by the herpes simplex virus Oct-1 coregulator VP16. OCA-B, however, interacts with a different surface of the DNA-bound Oct-1 POU domain, interacting with both the POU(S) and POU(H) domains and the center of the ATGCAAAT octamer sequence. The OCA-B and VP16 interactions with the Oct-1 POU domain are sufficiently different to permit OCA-B and VP16 to bind the Oct-1 POU domain simultaneously. These results emphasize the structural versatility of the Oct-1 POU domain in its interaction with coregulators.

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