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.

The Long Road to Understanding RNAPII Transcription Initiation and Related Syndromes

2021 ◽  
Vol 90 (1) ◽  
pp. 193-219
Author(s):  
Emmanuel Compe ◽  
Jean-Marc Egly
Keyword(s):  
Transcription Factors ◽  
Rna Polymerase Ii ◽  
Chromatin Remodeling ◽  
Transcription Initiation ◽  
Rna Synthesis ◽  
Regulatory Elements ◽  
Initiation Mechanism ◽  
Protein Coding ◽  
Core Promoters ◽  
General Transcription Factors

In eukaryotes, transcription of protein-coding genes requires the assembly at core promoters of a large preinitiation machinery containing RNA polymerase II (RNAPII) and general transcription factors (GTFs). Transcription is potentiated by regulatory elements called enhancers, which are recognized by specific DNA-binding transcription factors that recruit cofactors and convey, following chromatin remodeling, the activating cues to the preinitiation complex. This review summarizes nearly five decades of work on transcription initiation by describing the sequential recruitment of diverse molecular players including the GTFs, the Mediator complex, and DNA repair factors that support RNAPII to enable RNA synthesis. The elucidation of the transcription initiation mechanism has greatly benefited from the study of altered transcription components associated with human diseases that could be considered transcription syndromes.

scholarly journals Definition of a Second Bacillus subtilis pur Regulon Comprising the pur and xpt-pbuX Operons plus pbuG, nupG (yxjA), and pbuE (ydhL)

2003 ◽  
Vol 185 (17) ◽  
pp. 5200-5209 ◽  
Author(s):  
Lars Engholm Johansen ◽  
Per Nygaard ◽  
Catharina Lassen ◽  
Yvonne Agersø ◽  
Hans H. Saxild
Keyword(s):  
Bacillus Subtilis ◽  
Amino Acid ◽  
Transcription Initiation ◽  
Indirect Evidence ◽  
Amino Acid Sequences ◽  
Common Mechanism ◽  
Nucleoside Transporter ◽  
Independent Manner ◽  
Stem Loop ◽  
Transcription Terminator

ABSTRACT In Bacillus subtilis expression of genes or operons encoding enzymes and other proteins involved in purine synthesis is affected by purine bases and nucleosides in the growth medium. The genes belonging to the PurR regulon (purR, purA, glyA, guaC, pbuO, pbuG, and the pur, yqhZ-folD, and xpt-pbuX operons) are controlled by the PurR repressor, which inhibits transcription initiation. Other genes are regulated by a less-well-described transcription termination mechanism that responds to the presence of hypoxanthine and guanine. The pur operon and the xpt-pbuX operon, which were studied here, are regulated by both mechanisms. We isolated two mutants resistant to 2-fluoroadenine in which the pur operon and the xpt-pbuX operon are expressed at increased levels in a PurR-independent manner. The mutations were caused by deletions that disrupted a potential transcription terminator structure located immediately upstream of the ydhL gene. The 5′ part of the ydhL leader region contained a 63-nucleotide (nt) sequence very similar to the 5′ ends of the leaders of the pur and xpt-pbuX operons. Transcripts of these regions may form a common tandem stem-loop secondary structure. Two additional genes with potential leader regions containing the 63-nt sequence are pbuG, encoding a hypoxanthine-guanine transporter, and yxjA, which was shown to encode a purine nucleoside transporter and is renamed nupG. Transcriptional lacZ fusions and mutations in the 63-nt sequence encoding the possible secondary structures provided evidence that expression of the pur and xpt-pbuX operons and expression of the ydhL, nupG, and pbuG genes are regulated by a common mechanism. The new pur regulon is designated the XptR regulon. Except for ydhL, the operons and genes were negatively regulated by hypoxanthine and guanine. ydhL was positively regulated. The derived amino acid sequence encoded by ydhL (now called pbuE) is similar to the amino acid sequences of metabolite efflux pumps. When overexpressed, PbuE lowers the sensitivity to purine analogs. Indirect evidence indicated that PbuE decreases the size of the internal pool of hypoxanthine. This explains why the hypoxanthine- and guanine-regulated genes are expressed at elevated levels in a mutant that overexpresses pbuE.

scholarly journals The Membrane-Bound H+-ATPase Complex Is Essential for Growth of Lactococcus lactis

2000 ◽  
Vol 182 (17) ◽  
pp. 4738-4743 ◽  
Author(s):  
Brian J. Koebmann ◽  
Dan Nilsson ◽  
Oscar P. Kuipers ◽  
Peter R. Jensen
Keyword(s):  
Amino Acid ◽  
Lactococcus Lactis ◽  
Transcription Initiation ◽  
Northern Blot Analysis ◽  
Promoter Sequence ◽  
Initiation Site ◽  
Amino Acid Sequences ◽  
Significant Homology ◽  
Atpase Subunits ◽  
Membrane Bound

ABSTRACT The eight genes which encode the (F1Fo) H+-ATPase in Lactococcus lactis subsp.cremoris MG1363 were cloned and sequenced. The genes were organized in an operon with the gene order atpEBFHAGDC; i.e., the order of atpE and atpB is reversed with respect to the more typical bacterial organization. The deduced amino acid sequences of the corresponding H+-ATPase subunits showed significant homology with the subunits from other organisms. Results of Northern blot analysis showed a transcript at approximately 7 kb, which corresponds to the size of theatp operon. The transcription initiation site was mapped by primer extension and coincided with a standard promoter sequence. In order to analyze the importance of the H+-ATPase forL. lactis physiology, a mutant strain was constructed in which the original atp promoter on the chromosome was replaced with an inducible nisin promoter. When grown on GM17 plates the resulting strain was completely dependent on the presence of nisin for growth. These data demonstrate that the H+-ATPase is essential for growth of L. lactis under these conditions.

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.

Conserved and divergent roles for members of the Snail family of transcription factors in the chick and mouse embryo

Development ◽  
1998 ◽  
Vol 125 (16) ◽  
pp. 3111-3121 ◽  
Author(s):  
M. Sefton ◽  
S. Sanchez ◽  
M.A. Nieto
Keyword(s):  
Transcription Factors ◽  
Amino Acid ◽  
Chick Embryo ◽  
Neural Crest ◽  
Family Member ◽  
Zinc Finger ◽  
Mouse Embryo ◽  
Amino Acid Sequences ◽  
Mouse Homologue ◽  
Snail Family

The members of the Snail family of zinc-finger transcription factors have been implicated in the formation of distinct tissues within the developing vertebrate and invertebrate embryo. Two members of this family have been described in higher vertebrates, Snail (Sna) and Slug (Slu), where they have been implicated in the formation of tissues such as the mesoderm and the neural crest. We have isolated the mouse homologue of the Slu gene enabling us to analyse and compare the amino acid sequences and the patterns of expression of both Sna and Slu in the chick and mouse. We have detected features in the sequences that allow the unequivocal ascription of any family member to the Sna or Slu subfamilies and we have observed that, during early stages of development, many of the sites of Slu and Sna expression in the mouse and chick embryo are swapped. Later in development, the sites of expression of Slu and Sna are conserved between these two species. These data, together with the data available in other species, lead us to propose that Slu and Sna arose as a duplication of an ancestor gene and that an extra duplication in the fish lineage has given rise to two Sna genes. Furthermore, several early sites of Slu and Sna expression have been swapped in the avian lineage. Our analysis of the Snail family may also shed new light on the origin of the neural crest.

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 Genome-Wide Identification and Characterization of bZIP Transcription Factors inBrassica oleraceaunder Cold Stress

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Indeok Hwang ◽  
Ranjith Kumar Manoharan ◽  
Jong-Goo Kang ◽  
Mi-Young Chung ◽  
Young-Wook Kim ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Amino Acid ◽  
Cold Stress ◽  
Stress Responses ◽  
Sequence Similarity ◽  
Amino Acid Sequences ◽  
Amino Acid Sequence Similarity ◽  
Sequencing Data ◽  
Cold Response ◽  
Bzip Transcription Factors

Cabbages (Brassica oleraceaL.) are an important vegetable crop around world, and cold temperature is among the most significant abiotic stresses causing agricultural losses, especially in cabbage crops. Plant bZIP transcription factors play diverse roles in biotic/abiotic stress responses. In this study, 119 putative BolbZIP transcription factors were identified using amino acid sequences from several bZIP domain consensus sequences. The BolbZIP members were classified into 63 categories based on amino acid sequence similarity and were also compared with BrbZIP and AtbZIP transcription factors. Based on this BolbZIP identification and classification, cold stress-responsiveBolbZIPgenes were screened in inbred lines,BN106andBN107, using RNA sequencing data and qRT-PCR. The expression level of the 3 genes,Bol008071,Bol033132, andBol042729, was significantly increased inBN107under cold conditions and was unchanged inBN106. The upregulation of these genes inBN107, a cold-susceptible inbred line, suggests that they might be significant components in the cold response. Among three identified genes,Bol033132has 97% sequence similarity toBra020735, which was identified in a screen for cold-related genes inB. rapaand a protein containing N-rich regions in LCRs. The results obtained in this study provide valuable information for understanding the potential function of BolbZIP transcription factors in cold stress responses.

scholarly journals A Ligand Binding Domain Mutation in the Mouse Glucocorticoid Receptor Functionally Links Chromatin Remodeling and Transcription Initiation

1999 ◽  
Vol 19 (12) ◽  
pp. 8146-8157 ◽  
Author(s):  
Lynn A. Sheldon ◽  
Catharine L. Smith ◽  
Jack E. Bodwell ◽  
Allan U. Munck ◽  
Gordon L. Hager
Keyword(s):  
Glucocorticoid Receptor ◽  
Ligand Binding ◽  
Chromatin Remodeling ◽  
Transcriptional Activation ◽  
Transcription Initiation ◽  
Activation Function ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Activation Process ◽  
Activation Domain

ABSTRACT We utilized the mouse mammary tumor virus (MMTV) long terminal repeat (LTR) in vivo to understand how the interaction of the glucocorticoid receptor (GR) with a nucleosome-assembled promoter allows access of factors required for the transition from a repressed promoter to a derepressed, transcriptionally competent promoter. A mutation (C644G) in the ligand binding domain (LBD) of the mouse GR has provided information regarding the steps required in the derepression/activation process and in the functional significance of the two major transcriptional activation domains, AF1 and AF2. The mutant GR activates transcription from a transiently transfected promoter that has a disordered nucleosomal structure, though significantly less well than the wild-type GR. With an integrated, replicated promoter, which is assembled in an ordered nucleosomal array, the mutant GR does not activate transcription, and it fails to induce chromatin remodeling of the MMTV LTR promoter, as indicated by nuclease accessibility assays. Together, these findings support a two-step model for the transition of a nucleosome-assembled, repressed promoter to its transcriptionally active, derepressed form. In addition, we find that the C-terminal GR mutation is dominant over the transcription activation function of the N-terminal GR activation domain. These findings suggest that the primary activation function of the C-terminal activation domain is different from the function of the N-terminal activation domain and that it is required for derepression of the chromatin-repressed MMTV promoter.

scholarly journals Mutational analysis of the transcription activation domain of RelA: identification of a highly synergistic minimal acidic activation module

1994 ◽  
Vol 14 (11) ◽  
pp. 7226-7234
Author(s):  
W S Blair ◽  
H P Bogerd ◽  
S J Madore ◽  
B R Cullen
Keyword(s):  
Amino Acid ◽  
Transcription Initiation ◽  
Mutational Analysis ◽  
Regulatory Protein ◽  
Transcription Activation ◽  
Sequence Information ◽  
Activation Domain ◽  
Phenylalanine Residue

The potent C-terminal activation domain of the RelA (p65) subunit of the cellular transcription factor NF-kappa B is shown to contain several discrete acidic activation modules. These short, approximately 11-amino-acid modules were able to give rise to only a low level of transcription activation when fused to the GAL4 DNA-binding domain as monomers. However, dimers and higher-order multimers activated the transcription of minimal promoter elements as effectively as the full-length RelA or VP16 activation domain. Therefore, this 11-amino-acid RelA-derived acidic module appears to contain all of the sequence information required to fully activate a target promoter element as long as it is presented in a form that permits functional synergy. Critical primary sequence requirements for acidic activation module function included a core phenylalanine residue and flanking bulky hydrophobic residues. Overall negative charge was necessary but not sufficient for function. While dimeric forms of the 11-amino-acid acidic activation module bound to either TFIIB or TATA-binding protein efficiently in vitro, a similarly charged peptide lacking the core phenylalanine residue failed to interact. Overall, these data demonstrate that the biological activity of the RelA activation domain is dependent on acidic activator sequences that are closely comparable to those detected in the activation domain of the viral VP16 regulatory protein. We hypothesize that the ability of these acidic activators to specifically interact with multiple components of the transcription initiation complex likely underlies the dramatic functional synergy exhibited by this class of activation domains in vivo.

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