scholarly journals The evolution of the 9aaTAD domain in Sp2 proteins: inactivation with valines and intron reservoirs

2019 ◽  
Author(s):  
Martin Piskacek ◽  
Marek Havelka ◽  
Kristina Jendruchova ◽  
Andrea Knight ◽  
Liam P. Keegan
Keyword(s):  
Transcription Factor ◽  
Amino Acid ◽  
Evolutionary History ◽  
Amino Acid Substitutions ◽  
Activation Domain ◽  
Activation Domains ◽  
Transactivation Domains ◽  
Sp1 Transcription Factor ◽  
Chordate Evolution ◽  
Transcription Activators

AbstractThe Sp1 transcription factor has been defined as glutamine-rich activator. The Nine amino acid TransActivation Domains (9aaTAD) have been identified in numerous transcription activators. Here, we identified the conserved 9aaTAD motif in the Sp1 and in all nine members of SP family with broad natural 9aaTAD variations. We showed by the amino acid substitutions that the glutamine residues are completely dispensable for 9aaTADs function. We described the 9aaTAD domains’ origin and evolutionary history. The ancestral Sp2 gene with inactive 9aaTAD has duplicated in early chordates and created new paralogs Sp1, Sp3 and Sp4. We discovered that the accumulation of valines in the 9aaTADs correlated with the domain inactivation. The Sp2 activation domain, whose dormancy have lasted over 100 million years during chordate evolution, enabled later diversification in the Sp1-4 clade, including both repressors and activators. The new paralogs Sp1 and Sp3 activation domains have regained their original activator function by loss of valines in their 9aaTADs.

Inhibition of Xbra transcription activation causes defects in mesodermal patterning and reveals autoregulation of Xbra in dorsal mesoderm

Development ◽  
1996 ◽  
Vol 122 (8) ◽  
pp. 2427-2435 ◽  
Author(s):  
F.L. Conlon ◽  
S.G. Sedgwick ◽  
K.M. Weston ◽  
J.C. Smith
Keyword(s):  
Transcription Activation ◽  
Zebrafish Embryos ◽  
Transcription Activator ◽  
Activation Domain ◽  
Activation Domains ◽  
Dorsal Mesoderm ◽  
Transcription Activators ◽  
Carboxy Terminal ◽  
Genetic Mutants ◽  
Axial Development

The Brachyury (T) gene is required for formation of posterior mesoderm and for axial development in both mouse and zebrafish embryos. In this paper, we first show that the Xenopus homologue of Brachyury, Xbra, and the zebrafish homologue, no tail (ntl), both function as transcription activators. The activation domains of both proteins map to their carboxy terminal regions, and we note that the activation domain is absent in two zebrafish Brachyury mutations, suggesting that it is required for gene function. A dominant-interfering Xbra construct was generated by replacing the activation domain of Xbra with the repressor domain of the Drosophila engrailed protein. Microinjection of RNA encoding this fusion protein allowed us to generate Xenopus and zebrafish embryos which show striking similarities to genetic mutants in mouse and fish. These results indicate that the function of Brachyury during vertebrate gastrulation is to activate transcription of mesoderm-specific genes. Additional experiments show that Xbra transcription activation is required for regulation of Xbra itself in dorsal, but not ventral, mesoderm. The approach described in this paper, in which the DNA-binding domain of a transcription activator is fused to the engrailed repressor domain, should assist in the analysis of other Xenopus and zebrafish transcription factors.

Activation domains of gene-specific transcription factors: are histones among their targets?

2004 ◽  
Vol 82 (4) ◽  
pp. 453-459 ◽  
Author(s):  
Alexandre M Erkine
Keyword(s):  
Transcription Factors ◽  
Amino Acid ◽  
Chromatin Remodeling ◽  
Transcription Initiation ◽  
Protein Complexes ◽  
Amino Acid Sequences ◽  
Gene Promoters ◽  
Activation Domain ◽  
Activation Domains ◽  
Multiple Protein

Activation domains of promoter-specific transcription factors are critical entities involved in recruitment of multiple protein complexes to gene promoters. The activation domains often retain functionality when transferred between very diverse eukaryotic phyla, yet the amino acid sequences of activation domains do not bear any specific consensus or secondary structure. Activation domains function in the context of chromatin structure and are critical for chromatin remodeling, which is associated with transcription initiation. The mechanisms of direct and indirect recruitment of chromatin-remodeling and histone-modifying complexes, including mechanisms involving direct interactions between activation domains and histones, are discussed.Key words: activation domain, transcription, chromatin, nucleosome.

scholarly journals Evolution of the activation domain in a Hox transcription factor

2018 ◽  
Vol 62 (11-12) ◽  
pp. 745-753 ◽  
Author(s):  
Ying Liu ◽  
Annie Huang ◽  
Rebecca M. Booth ◽  
Gabriela Geraldo Mendes ◽  
Zabeena Merchant ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Intrinsically Disordered Protein ◽  
Transcription Activation ◽  
Specific Protein ◽  
Amino Acid Sequences ◽  
Activation Domain ◽  
Mutant Proteins ◽  
Activation Domains ◽  
Intrinsically Disordered

Linking changes in amino acid sequences to the evolution of transcription regulatory domains is often complicated by the low sequence complexity and high mutation rates of intrinsically disordered protein regions. For the Hox transcription factor Ultrabithorax (Ubx), conserved motifs distributed throughout the protein sequence enable direct comparison of specific protein regions, despite variations in the length and composition of the intervening sequences. In cell culture, the strength of transcription activation by Drosophila melanogaster Ubx correlates with the presence of a predicted helix within its activation domain. Curiously, this helix is not preserved in species more divergent than flies, suggesting the nature of transcription activation may have evolved. To determine whether this helix contributes to Drosophila Ubx function in vivo, wild-type and mutant proteins were ectopically expressed in the developing wing and the phenotypes evaluated. Helix mutations alter Drosophila Ubx activity in the developing wing, demonstrating its functional importance in vivo. The locations of activation domains in Ubx orthologues were identified by testing the ability of truncation mutants to activate transcription in yeast one-hybrid assays. In Ubx orthologues representing 540 million years of evolution, the ability to activate transcription varies substantially. The sequence and the location of the activation domains also differ. Consequently, analogous regions of Ubx orthologues change function over time, and may activate transcription in one species, but have no activity, or even inhibit transcription activation in another species. Unlike homeodomain-DNA binding, the nature of transcription activation by Ubx has substantially evolved.

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.

The Oct-2 glutamine-rich and proline-rich activation domains can synergize with each other or duplicates of themselves to activate transcription

1994 ◽  
Vol 14 (9) ◽  
pp. 6046-6055
Author(s):  
M Tanaka ◽  
W M Clouston ◽  
W Herr
Keyword(s):  
Amino Acid ◽  
Dna Binding ◽  
Transcriptional Activation ◽  
Activation Domain ◽  
Activation Domains ◽  
Amino Acid Region ◽  
Pou Domain ◽  
Octamer Motif ◽  
P Domain ◽  
Acid Region

The B-cell POU homeodomain protein Oct-2 contains two transcriptional activation domains, one N terminal and the other C terminal of the central DNA-binding POU domain. The synergistic action of these two activation domains makes Oct-2 a more potent activator of mRNA promoters than the related broadly expressed octamer motif-binding protein Oct-1, which contains an N-terminal but not a C-terminal Oct-2-like activation domain. Both Oct-2 mRNA promoter activation domains were delineated by truncation analysis: the N-terminal Q domain is a 66-amino-acid region rich in glutamines, and the C-terminal P domain is a 42-amino-acid region rich in prolines. The Q and P domains synergized with each other or duplicates of themselves, independently of their N-terminal or C-terminal position relative to the POU domain. The C-terminal P domain, which differentiates Oct-2 from Oct-1, also activated transcription in conjunction with the heterologous GAL4 DNA-binding domain. Oct-2 thus contains three modular functional units, the DNA-binding POU domain and the two P and Q activation domains. An electrophoretic mobility shift assay with a variety of these Oct-2 activators revealed a distinct complex called QA that was dependent on the presence of an active glutamine-rich activation domain and migrated more slowly than the Oct-2-DNA complexes. Formation of the QA complex is consistent with interaction of the glutamine-rich activation domains with a regulatory protein important for the process of transcriptional activation.

scholarly journals The Oct-2 glutamine-rich and proline-rich activation domains can synergize with each other or duplicates of themselves to activate transcription.

1994 ◽  
Vol 14 (9) ◽  
pp. 6046-6055 ◽  
Author(s):  
M Tanaka ◽  
W M Clouston ◽  
W Herr
Keyword(s):  
Amino Acid ◽  
Dna Binding ◽  
Transcriptional Activation ◽  
Activation Domain ◽  
Activation Domains ◽  
Amino Acid Region ◽  
Pou Domain ◽  
Octamer Motif ◽  
P Domain ◽  
Acid Region

The B-cell POU homeodomain protein Oct-2 contains two transcriptional activation domains, one N terminal and the other C terminal of the central DNA-binding POU domain. The synergistic action of these two activation domains makes Oct-2 a more potent activator of mRNA promoters than the related broadly expressed octamer motif-binding protein Oct-1, which contains an N-terminal but not a C-terminal Oct-2-like activation domain. Both Oct-2 mRNA promoter activation domains were delineated by truncation analysis: the N-terminal Q domain is a 66-amino-acid region rich in glutamines, and the C-terminal P domain is a 42-amino-acid region rich in prolines. The Q and P domains synergized with each other or duplicates of themselves, independently of their N-terminal or C-terminal position relative to the POU domain. The C-terminal P domain, which differentiates Oct-2 from Oct-1, also activated transcription in conjunction with the heterologous GAL4 DNA-binding domain. Oct-2 thus contains three modular functional units, the DNA-binding POU domain and the two P and Q activation domains. An electrophoretic mobility shift assay with a variety of these Oct-2 activators revealed a distinct complex called QA that was dependent on the presence of an active glutamine-rich activation domain and migrated more slowly than the Oct-2-DNA complexes. Formation of the QA complex is consistent with interaction of the glutamine-rich activation domains with a regulatory protein important for the process of transcriptional activation.

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 Activation of transcription by PU.1 requires both acidic and glutamine domains.

1996 ◽  
Vol 16 (1) ◽  
pp. 390-397 ◽  
Author(s):  
M J Klemsz ◽  
R A Maki
Keyword(s):  
Amino Acids ◽  
Transcription Factor ◽  
B Lymphocyte ◽  
Significant Loss ◽  
Activation Domain ◽  
Activation Domains ◽  
Amino Terminal ◽  
Activation Of Transcription ◽  
Ets Family ◽  
Series Of Experiments

The B-lymphocyte- and macrophage-specific transcription factor PU.1 is a member of the ets family of proteins. To understand how PU.1 functions as a transcription factor, we initiated a series of experiments to define its activation domain. Using deletion analysis, we showed that the activation domain of PU.1 is located in the amino-terminal half of the protein. Within this region, we identified three acidic subdomains and one glutamine-rich subdomain. The deletion of any of these subdomains resulted in a significant loss in the ability of PU.1 to transactivate in cotransfection studies. Amino acid substitution analysis showed that the activation of transcription by PU.1 requires acidic residues between amino acids 7 and 74 and a group of glutamine residues between amino acids 75 and 84. These data show that PU.1 contains two types of known activation domains and that both are required for maximal transactivation.

scholarly journals Gal4 activation domain 9aaTAD could be inactivated by adjacent mini-inhibitory domain and reactivated by distal re-activation domain

2017 ◽  
Author(s):  
Martin Piskacek ◽  
Marek Havelka ◽  
Martina Rezacova ◽  
Andrea Knight
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Small Region ◽  
Inhibitory Effect ◽  
Prediction Algorithm ◽  
Transactivation Domain ◽  
Activation Domain ◽  
Activation Domains ◽  
Gal4 Activation Domain ◽  
Inhibitory Domain

AbstractThe characterisation of the activation domains started three decades ago with Gcn4 and Gal4 activators. The amorphous character of the activation domains strongly hindered their definition. Moreover, during the attempts to localise the Gal4 activation domain, the artificial peptides, an unintended consequence of cloning, were responsible for artificial transcriptional activity of the several Gal4 constructs. These artefacts produced enormous experimental bias and misconception. The presence of inhibitory domains in some Gal4 constructs made the misperception even worse. Previously, we reported that the nine amino acid transactivation domain, 9aaTAD, is the exclusive activation domain in the Gal4 protein. The activation domain 9aaTAD could be identified in Gal4 paralogs Oaf1, Pip2, Pdr1, Pdr3 and other activators p53, E2A and MLL. Surprisingly, the activation domain 9aaTAD was reported as misconception for Gal4 activator. Here we demonstrated that small region of 10 amino acids adjacent to the Gal4 activation domain 9aaTAD is an inhibitory domain, which the authors included in their constructs. Moreover, we identified Gal4 region, which was able to the reverse the inhibitory effect. The 9aaTAD re-activation domain was localized to the 13 amino acid long region. In this report we clarified the numerous confusions and rebutted supposed 9aaTAD misconception.SummaryThe activation domain 9aaTAD has decisive function in Gal4 activation. Gal4 activation domain 9aaTAD could be inhibited by adjacent region of 10 amino acids. The inhibited Gal4 activation domain 9aaTAD could be reactivated by 13 amino acid long Gal4 region. The activation domains 9aaTAD could be identified by our 9aaTAD prediction algorithm, especially in the Gal4 family.

scholarly journals Many Amino Acid Substitutions in a Hypoxia-inducible Transcription Factor (HIF)-1α-like Peptide Cause Only Minor Changes in Its Hydroxylation by the HIF Prolyl 4-Hydroxylases

2004 ◽  
Vol 279 (53) ◽  
pp. 55051-55059 ◽  
Author(s):  
Dongxia Li ◽  
Maija Hirsilä ◽  
Peppi Koivunen ◽  
Mitchell C. Brenner ◽  
Leon Xu ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Amino Acid ◽  
Amino Acid Substitutions
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