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Results for “transcription factor evolution”

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PubMed1998

The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins.

The c-Myc and E2F transcription factors are among the most potent regulators of cell cycle progression in higher eukaryotes. This report describes the isolation of a novel, highly conserved 434 kDa protein, designated TRRAP, which interacts specifically with the c-Myc N terminus and has homology to the ATM/PI3-kinase family. TRRAP also interacts specifically with the E2F-1 transactivation domain. Expression of transdominant mutants of the TRRAP protein or antisense RNA blocks c-Myc- and E1A-mediated oncogenic transformation. These data suggest that TRRAP is an essential cofactor for both the c-Myc and E1A/E2F oncogenic transcription factor pathways.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Transcriptional control elements of the rat thymidylate synthase promoter: evolutionary conservation of regulatory features.

The sequence elements that are important for the transcription and regulation of the rat thymidylate synthase (TS) gene were analyzed. The rat TS promoter lacks a TATA box and directs transcriptional initiation at multiple sites between 60 and 20 nt upstream of the AUG translational start codon. Promoter deletion analyses showed that the region between -100 and -42 nt relative to the AUG codon was both necessary and sufficient for high level promoter activity and was designated the essential promoter region. The essential region also had bidirectional promoter activity. Site-directed mutagenesis revealed that four elements were especially important for promoter activity. These include Ets motifs at -85 and -50, an Sp1 motif at -80, and an LSF motif that overlapped the upstream Ets and Sp1 motifs. Inactivation of E2F motifs that are upstream and downstream of the essential promoter region had no measurable effect on promoter activity in transient transfection assays. The rat TS promoter region directed S-phase-specific expression of a stably transfected minigene if a spliceable intron was included in the transcribed region. When the intron was deleted or the E2F motifs were inactivated, expression of the minigene changed very little during the G1 to S transition.

Animals↗

PubMed2004

[Nucleotide polymorphism in the drought induced transcription factor CBF4 region of Arabidopsis thaliana and its molecular evolution analyses].

Intraspecific nucleotide polymorphism in the drought induced transcription factor CBF4 region of Arabidopsis thaliana was analyzed with 17 core accessions growing in different ecoclimate. High density of single nucleotide polymorphism (SNP) and insertion/deletion (Indel) were found, on average 1 SNP per 35.8 bp and 1 Indel per 143 bp. Nucleotide polymorphism in non-coding region was three times higher than that in coding region. In coding region of CBF4, SNP frequency is one SNP per 96.4 bp, one nonsynonymous mutation was detected from 25 av, 203 av and 244 av accessions, which is the 205th site amino acid variation: gly <--> val caused by the 1034th site (corresponding to 19,696 site nucleotide of GenBank No. AB015478 as 1) nucleotide variation: G <--> T. Statistical result of nucleotide diversity showed that linkage disequilibrium (LD) existed in large-scale region of CBF4 and recombination event was also detected in 5' non-coding region. Identical to the results of other genes of Arabidopsis, different regions of the gene were seemingly under different selective pressures. Balancing selection resulted in high nucleotide diversity in 3' non-coding region, and the neutral mutation hypothesis can explain the DNA polymorphism in coding region, whereas, nature positive selection in the population affected nucleotide variation in 5' non-coding region of gene.

Arabidopsis↗

PubMed2005

Evolution of vertebrate E protein transcription factors: comparative analysis of the E protein gene family in Takifugu rubripes and humans.

E proteins are essential for B lymphocyte development and function, including immunoglobulin (Ig) gene rearrangement and expression. Previous studies of B cells in the channel catfish (Ictalurus punctatus) identified E protein homologs that are capable of binding the muE5 motif and driving a strong transcriptional response. There are three E protein genes in mammals, HEB (TCF12), E2A (TCF3), and E2-2 (TCF4). The major expressed E proteins found in catfish B cells are homologs of HEB and of E2A. Here we sought to define the complete family of E protein genes in a teleost fish, Takifugu rubripes, taking advantage of the completed genome sequence. The catfish CFEB (HEB homolog) sequence identified homologous E-protein-encoding sequences in five scaffolds in the Takifugu genome database. Detailed comparative analysis with the human genome revealed the presence of five E protein homologs in Takifugu. Single genes orthologous to HEB and to E2-2 were identified. In contrast, two members of the E2A gene family were identified in Takifugu; one of these shows the alternative processing of transcripts that identifies it as the ortholog of the E12/E47-encoding mammalian E2A gene, whereas the second Takifugu E2A gene has no predicted alternative splice products. A novel fifth E protein gene (EX) was identified in Takifugu. Phylogenetic analysis revealed four E protein branches among vertebrates: EX, E2A, HEB, and E2-2.

Animals↗

PubMed2005

Association of anophthalmia and esophageal atresia: four new cases identified by the anophthalmia/microphthalmia clinical registry.

We report four new cases of the rare association of anophthalmia and esophageal atresia. There are only nine cases previously reported in the literature with this association. Our cases appear to be distinct from those already reported, thus increasing the number of cases to thirteen. Advances in developmental biology have shown that mutations in developmental genes active early in embryogenesis can lead to birth defects in multiple, seemingly unrelated systems. The network of genes that directs development has been highly conserved through evolution. Several transcription factors have been shown to be important in regulating eye development. Mutations in these developmental genes may be the cause of this clinical association.

Abnormalities, Multiple↗

PubMed2006

Hsc70 contacts helix III of the J domain from polyomavirus T antigens: addressing a dilemma in the chaperone hypothesis of how they release E2F from pRb.

Hsc70's expected binding site on helix II of the J domain of T antigens appears to be blocked in its structure bound to tumor suppressor pRb. We used NMR to map where mammalian Hsc70 binds the J domain of murine polyomavirus T antigens (PyJ). The ATPase domain of Hsc70 unexpectedly has its biggest effects on the NMR peak positions of the C-terminal end of helix III of PyJ. The Hsc70 ATPase domain protects the C-terminal end of helix III of PyJ from an uncharged paramagnetic probe of chelated Gd(III), clearly suggesting the interface. Effects on the conserved HPD loop and helix II of PyJ are smaller. The NMR results are supported by a novel assay of Hsc70's ATP hydrolysis showing that mutations of surface residues in PyJ helix III impair PyJ-dependent stimulation of Hsc70 activity. Evolutionary trace analysis of J domains suggests that helix III usually may join helix II in contributing specificities for cognate hsp70s. Our novel evidence implicating helix III differs from evidence that Escherichia coli DnaK primarily affects helix II and the HPD loop of DnaJ. We find the pRb-binding fragment of E2F1 to be intrinsically unfolded and a good substrate for Hsc70 in vitro. This suggests that E2F1 could be a substrate for Hsc70 recruited by T antigen to an Rb family member. Importantly, our results strengthen the chaperone hypothesis for E2F release from an Rb family member by Hsc70 recruited by large T antigen. That is, it now appears that Hsc70 can freely access helix III and the HPD motif of large T antigen bound to an Rb family member.

Adenosine Triphosphatases↗

PubMed1990

Structure and evolution of a human erythroid transcription factor.

Vertebrate erythroid cells contain a tissue-specific transcription factor referred to as Eryf 1 (ref. 1), GF-1 (ref. 2) or NF-E1 (ref. 3), for which binding sites are widely distributed in the promoters and enhancers of the globin gene family, and of other erythroid-specific genes. Aberrant binding of the human factor to a mutant site has been implicated in one form of hereditary persistence of fetal haemoglobin (HPFH; ref. 2). The complementary DNAs for both the chicken cEryf 1 (ref. 11) and mouse mEryf 1 (ref. 12) encoding genes have recently been cloned. We report here the cloning of the cDNA for the human Eryf 1 encoding gene. The central third of the hEryf 1 cDNA, containing two 'finger' motifs, is almost identical to that of chicken or mouse. The amino-and carboxy-terminal thirds of the human protein are similar to those of mouse, but are strikingly different from the corresponding domains in chicken. The evidence indicates that these erythroid regulatory factors evolved from a common precursor composed of two distinct kinds of repeated domains, which subsequently evolved at greatly different rates.

Amino Acid Sequence↗

PubMed2003

[Beyond glucocorticoids, retinoids and vitamin D--the evolution of nuclear hormone type transcription factor targeting in the skin].

Nuclear hormone receptors are ligand-dependent transcription factors. The class of nuclear hormone receptors that form heterodimers with retinoid X receptor includes members that are well established targets of current dermatological therapeutics such as the retinoic acid receptor (RAR) and the vitamin D receptor (VDR) as well as more recently discovered receptors including the peroxisome proliferator-activated receptors (PPAR) and the liver X receptor (LXR). After ligand activation (often lipid metabolites), these intracellular receptors exert their functions by binding to specific response elements in regulatory sequences of target genes, preferentially those involved in differentiation, energy expenditure and lipid metabolism. A number of selective activators has been developed by combinational chemistry, initially for their anti-diabetic and lipid lowering properties as well as their ability to regulate bile acid and drug metabolism. However, these activators also have marked effects on cutaneous homeostasis. Therefore, these compounds have important implications for dermatological therapy. In this review, the clinical implications of the more recently discovered members of the nuclear hormone receptor family are discussed.

Animals↗

PubMed2016

Substituting mouse transcription factor Pou4f2 with a sea urchin orthologue restores retinal ganglion cell development.

Pou domain transcription factor Pou4f2 is essential for the development of retinal ganglion cells (RGCs) in the vertebrate retina. A distant orthologue of Pou4f2 exists in the genome of the sea urchin (class Echinoidea) Strongylocentrotus purpuratus (SpPou4f1/2), yet the photosensory structure of sea urchins is strikingly different from that of the mammalian retina. Sea urchins have no obvious eyes, but have photoreceptors clustered around their tube feet disc. The mechanisms that are associated with the development and function of photoreception in sea urchins are largely unexplored. As an initial approach to better understand the sea urchin photosensory structure and relate it to the mammalian retina, we asked whether SpPou4f1/2 could support RGC development in the absence of Pou4f2. To answer this question, we replaced genomic Pou4f2 with an SpPou4f1/2 cDNA. In Pou4f2-null mice, retinas expressing SpPou4f1/2 were outwardly identical to those of wild-type mice. SpPou4f1/2 retinas exhibited dark-adapted electroretinogram scotopic threshold responses, indicating functionally active RGCs. During retinal development, SpPou4f1/2 activated RGC-specific genes and in S. purpuratus, SpPou4f2 was expressed in photoreceptor cells of tube feet in a pattern distinct from Opsin4 and Pax6. Our results suggest that SpPou4f1/2 and Pou4f2 share conserved components of a gene network for photosensory development and they maintain their conserved intrinsic functions despite vast morphological differences in mouse and sea urchin photosensory structures.

Animals↗

PubMed2003

Signaling receptome: a genomic and evolutionary perspective of plasma membrane receptors involved in signal transduction.

Intercellular communication in multicellular organisms requires the relay of extracellular signals by cell surface proteins to the interiors of cells. The availability of genome sequences from humans and several model organisms has facilitated the identification of several human plasma membrane receptor families and allowed the analysis of their phylogeny. This review provides a global categorization of most known signal transduction-associated receptors as enzymes, recruiters, and latent transcription factors. The evolution of known families of human plasma membrane signaling receptors was traced in current literature and validated by sequence relatedness. This global analysis reveals themes that recur during receptor evolution and allows the formulation of hypotheses for the origins of receptors. The human receptor families involved in signaling (with the exception of channels) are presented in the Human Plasma Membrane Receptome database.

Animals↗

PubMed2004

Differential cytoplasmic mRNA localisation adjusts pair-rule transcription factor activity to cytoarchitecture in dipteran evolution.

Establishment of segmental pattern in the Drosophila syncytial blastoderm embryo depends on pair-rule transcriptional regulators. mRNA transcripts of pair-rule genes localise to the apical cytoplasm of the blastoderm via a selective dynein-based transport system and signals within their 3'-untranslated regions. However, the functional and evolutionary significance of this process remains unknown. We have analysed subcellular localisation of mRNAs from multiple dipteran species both in situ and by injection into Drosophila embryos. We find that although localisation of wingless transcripts is conserved in Diptera, localisation of even-skipped and hairy pair-rule transcripts is evolutionarily labile and correlates with taxon-specific changes in positioning of nuclei. We show in Drosophila that localised pair-rule transcripts target their proteins in close proximity to the nuclei and increase the reliability of the segmentation process by augmenting gene activity. Our data suggest that mRNA localisation signals in pair-rule transcripts affect nuclear protein uptake and thereby adjust gene activity to a variety of dipteran blastoderm cytoarchitectures.

3' Untranslated Regions↗

PubMed2006

Detecting the limits of regulatory element conservation and divergence estimation using pairwise and multiple alignments.

BACKGROUND: Molecular evolutionary studies of noncoding sequences rely on multiple alignments. Yet how multiple alignment accuracy varies across sequence types, tree topologies, divergences and tools, and further how this variation impacts specific inferences, remains unclear. RESULTS: Here we develop a molecular evolution simulation platform, CisEvolver, with models of background noncoding and transcription factor binding site evolution, and use simulated alignments to systematically examine multiple alignment accuracy and its impact on two key molecular evolutionary inferences: transcription factor binding site conservation and divergence estimation. We find that the accuracy of multiple alignments is determined almost exclusively by the pairwise divergence distance of the two most diverged species and that additional species have a negligible influence on alignment accuracy. Conserved transcription factor binding sites align better than surrounding noncoding DNA yet are often found to be misaligned at relatively short divergence distances, such that studies of binding site gain and loss could easily be confounded by alignment error. Divergence estimates from multiple alignments tend to be overestimated at short divergence distances but reach a tool specific divergence at which they cease to increase, leading to underestimation at long divergences. Our most striking finding was that overall alignment accuracy, binding site alignment accuracy and divergence estimation accuracy vary greatly across branches in a tree and are most accurate for terminal branches connecting sister taxa and least accurate for internal branches connecting sub-alignments. CONCLUSION: Our results suggest that variation in alignment accuracy can lead to errors in molecular evolutionary inferences that could be construed as biological variation. These findings have implications for which species to choose for analyses, what kind of errors would be expected for a given set of species and how multiple alignment tools and phylogenetic inference methods might be improved to minimize or control for alignment errors.

Binding Sites↗

PubMed1997

Rel/NF-kappa B transcription factors and I kappa B inhibitors: evolution from a unique common ancestor.

From the sequences of Rel/NF-kappa B and I kappa B proteins, we constructed an alignment of their Rel Homology Domain (RHD) and ankyrin repeat domain. Using this alignment, we performed tree reconstruction with both distance matrix and parsimony analysis and estimated the branching robustness using bootstrap resampling methods. We defined four subfamilies of Rel/NF-kappa B transcription factors: (i) cRel, RelA, RelB, Dorsal and Dif; (ii) NF-kappa B1 and NF-kappa B2; (iii) Relish and (iv) NF-AT factors, the most divergent members. Subfamilies I and II are clustered together whereas Relish diverged earlier than other Rel/NF-kappa B proteins. Three subfamilies of I kappa B inhibitors were also defined: (i) NF-kappa B1 and NF-kappa B2; (ii) close to subfamily I, the short I kappa B proteins I kappa B alpha, I kappa B beta and Bcl-3; (iii) Relish that diverged earlier than other I kappa B inhibitors. Our definition of groups and subfamilies fits to structural and functional features of the Rel/NF-kappa B and I kappa B proteins. We also showed that ankyrin repeats of NF-kappa B1, NF-kappa B2 and Relish are short I kappa B-specific ankyrin motifs. These proteins defining a link between Rel/NF-kappa B and I kappa B families, we propose that all these factors evolved from a common ancestral RHD-ankyrin structure within a unique superfamily, explaining the specificities of interaction between the different Rel/NF-kappa B dimers and the various I kappa B inhibitors.

Amino Acid Sequence↗

PubMed2006

The family of DOF transcription factors: from green unicellular algae to vascular plants.

This article deals with the origin and evolution of the DOF transcription factor family through a phylogenetic analysis of those DOF sequences identified from a variety of representative organisms from different taxonomic groups: the green unicellular alga Chlamydomonas reinhardtii, the moss Physcomitrella patens, the fern Selaginella moellendorffii, the gymnosperm Pinus taeda, the dicotyledoneous Arabidopsis thaliana and the monocotyledoneous angiosperms Oryza sativa and Hordeum vulgare. In barley, we have identified 26 different DOF genes by sequence analyses of clones isolated from the screening of genomic libraries and of ESTs, whereas a single DOF gene was identified by bioinformatics searches in the Chlamydomonas genome. The phylogenetic analysis groups all these genes into six major clusters of orthologs originated from a primary basal grade. Our results suggest that duplications of an ancestral DOF, probably formed in the photosynthetic eukaryotic ancestor, followed by subsequent neo-, sub-functionalization and pseudogenization processes would have triggered the expansion of the DOF family. Loss, acquisition and shuffling of conserved motifs among the new DOFs likely underlie the mechanism of formation of the distinct subfamilies.

Algal Proteins↗

PubMed2026

Molecular evolution and immune expression analysis of ELF transcription factors in Lethenteron reissneri.

As important members of the ETS superfamily, the E74-like factor (ELF) transcription factor family regulates gene transcription through a conserved ETS domain and plays critical roles in immune regulation. However, the evolutionary characteristics and functions of this family in lampreys (Lethenteron reissneri) remain unclear. In this study, the ELF gene family of lampreys (Lr-ELF1, Lr-ELF2, Lr-ELF3, and Lr-ELF5) was systematically identified, and their molecular evolutionary features and immune response functions were investigated. Phylogenetic analysis revealed evolutionary characteristics reflecting the transition from jawless to jawed vertebrates. Domain architecture, gene structure, and three-dimensional structural analyses indicated that these genes appear to be conserved among vertebrates, with their three-dimensional structures showing high similarity to the core secondary structural elements of human homologous proteins. Synteny analysis demonstrated significant differences in the genomic neighborhoods of ELF genes between lampreys and jawed vertebrates. Quantitative real-time PCR (qRT-PCR) was performed with three biological and three technical replicates; relative expression levels were calculated using the ΔCt method, and statistical analysis was carried out with GraphPad Prism 9. Quantitative real-time PCR (qRT-PCR) results suggested that the ELF gene family may be involved in immune defense. This study not only enriches our understanding of the evolution of ELF genes but also provides new insights into the roles of lamprey ELFs in immune defense.

Animals↗

PubMed1994

A model for gene evolution of the ets-1/ets-2 transcription factors based on structural and functional homologies.

The chicken c-ets-1 locus encodes two transcription factors, p54c-ets-1 and p68c-ets-1 that differ in their N-termini, encoded respectively by the I54 and alpha beta exons. p68c-ets-1 equivalents are only found in birds and reptiles while p54c-ets-1 is widely conserved in vertebrates, from amphibians to mammals. Thus, the classical view concerning the evolution of the c-ets-1 gene has been to consider that I54 is of ancient origin whereas alpha and beta, which provide an additional activating domain in p68c-ets-1, would have been acquired much more recently. Sequencing the alpha and beta exons in various species pinpointed a highly conserved region of 13 amino acids which is rich in acidic and hydrophobic residues, a feature of some other transactivating domains. Strikingly, this subdomain is also present in the otherwise unrelated N-terminal activating region of p58c-ets-2 and was thus named BEC for Ets-1-beta/Ets-2-Conserved sequence. Moreover, the two N-termini share the BEC sequence at a homologous position in their highly similar genomic organization indicating a common origin. This structural homology underlies a functional similarity since fusion of the heterologous GAL4 DNA-binding domain with either of the two isolated domains demonstrates that BEC is essential in both cases for the transactivating activity. The function of the alpha beta domain in the context of p68c-ets-1 also strictly depends on the presence of the BEC sequence. Finally, the whole N-terminus of p58c-ets-2 can functionally substitute for its counterpart in p68c-ets-1 further demonstrating that p68c-ets-1 and p58c-ets-2 are structurally and functionally more closely related than previously thought. Besides, we also found BEC in the N-terminus of the Drosophila pointed gene which may be considered as closely related to the uncommitted 'ets1/2' common ancestor. These data demonstrate that the alpha and beta exons are not a recent and specific acquisition but stem, like the p58c-ets-2 N-terminus, from the invertebrate unduplicated 'ets 1/2' gene. This work unravels a new model for the ets-1/ets-2 gene's evolution, based for the first time on both structural and functional evidences. Accordingly, p68c-ets-1 and p58c-ets-2 are the direct descendants of the ancestral 'ets1/2' gene whereas I54 may have been acquired as a second promoter in the c-ets-1 gene after the duplication. Indeed, I54 is not found in the Drosophila pointed gene. The high degree of similarity, and hence of functional redundancy, between p68c-ets-1 and p58c-ets-2 may have led to the rapid divergence (and even loss in mammals) of alpha and beta during evolution whereas I54, which provided a novel function unique to c-ets-1, was maintained within the presently widespread p54c-ets-1 version.

Amino Acid Sequence↗

PubMed1998

Molecular evolution of the Myb family of transcription factors: evidence for polyphyletic origin.

The Myb family of proteins is a group of functionally diverse transcriptional activators found in both plants and animals that is characterized by a conserved DNA-binding domain of approximately 50 amino acids. Phylogenetic analyses of amino acid sequences of this family of proteins portray very disparate evolutionary histories in plants and animals. Animal Myb proteins have diverged from a common ancestor, while plants appear related only within the DNA-binding domain. Results imply a pattern of modular evolution of the Myb proteins centering on the possession of a helix-turn-helix motif. Based on this it is suggested that Myb proteins are a polyphyletic group related only by a "Myb-box" DNA-binding motif.

Animal Population Groups↗

PubMed2006

Eukaryotic transcription factors in plastids--Bioinformatic assessment and implications for the evolution of gene expression machineries in plants.

The expression of genes in higher plant chloroplasts includes a complex transcriptional regulation which can be explained only in part with the action of the actually known components of the transcriptional machinery. This suggests the existence of still unknown important regulatory factors which influence chloroplast transcription. In order to test if such factors could exist we performed in silico analyses of Arabidopsis genes encoding putative transcription factors looking for putative N-terminal chloroplast transit peptides in the amino acid sequences. Our results suggest that 48 (and maybe up to 100) transcription factors of eukaryotic origin are likely to be imported into plastids. None of them has been described yet. This set of transcription factors highly expands the actually known regulation capacity of the chloroplast transcription machinery and provides a possible explanation for the complex initiation patterns of chloroplast transcripts. As consequence of a massive import of eukaryotic transcription factors a comprehensive reconstruction of the ancient prokaryotic gene expression machinery must be assumed resulting in a novel compatible combination of eukaryotic and prokaryotic protein components. In turn, the opposite process has been induced in the nucleus by the integration of prokaryotic components of the plastid ancestor via its loss of genes during endosymbiosis. Thus, a mutual exchange of regulatory factors, i.e. transcription factors occurred which resulted in the unique signalling network of today's plants. An evolutionary model of how this could have emerged during endosymbiosis in a timely coordinated manner is proposed.

Arabidopsis↗