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At least 1,315 records · Page 73Linked to original sources
PubMed2007

Engineering promoter regulation.

Systems for easily controlled, conditional induction or repression of gene expression are indispensable tools in fundamental research and industrial-scale biotechnological applications. Both native and rationally designed inducible promoters have been widely used for this purpose. However, inherent regulation modalities or toxic, expensive or inconvenient inducers can impose limitations on their use. Tailored promoters with user-specified regulatory properties would permit sophisticated manipulations of gene expression. Here, we report a generally applicable strategy for the directed evolution of promoter regulation. Specifically, we applied random mutagenesis and a multi-stage flow cytometry screen to isolate mutants of the oxygen-responsive Saccharomyces cerevisiae DAN1 promoter. Two mutants were isolated which were induced under less-stringent anaerobiosis than the wild-type promoter enabling induction of gene expression in yeast fermentations simply by oxygen depletion during cell growth. Moreover, the engineered promoters showed a markedly higher maximal expression than the unmutated DAN1 promoter, under both fastidious anaerobiosis and microaerobisois.

Aerobiosis↗
PubMed2005

PAR proteins and the cytoskeleton: a marriage of equals.

The PAR proteins are a group of widely conserved regulators of polarity, many of which are asymmetrically localized in polarized cells. Recent work shows that distinct modes of actomyosin- and microtubule-based transport contribute to the establishment of PAR asymmetries in different cell types. Cross-regulatory interactions among PAR proteins and with other conserved polarity complexes stabilize asymmetries once they form, and shape the evolution of PAR protein distributions in response to cytoskeletal transport or other polarizing inputs. The PAR proteins in turn modulate the actomyosin and microtubule cytoskeletons. In some cases, this is a form of feedback control, central to the establishment and maintenance of PAR asymmetries. In others, it underlies the elaboration of functional cell polarity.

Actomyosin↗
PubMed2004

2S storage protein gene of Douglas-fir: characterization and activity of promoter in transgenic tobacco seeds.

To date a few sequences regulating expression of conifer seed-specific genes have been reported. To characterize Douglas-fir (Pseudotsuga menziesii [Mirb] Franco) 2S albumin storage protein genes, a genomic DNA sequence containing upstream promoter sequences was isolated by screening a Douglas-fir genomic library. Sequence analysis of the Douglas-fir gPm2S1 promoter revealed the presence of RY-repeated elements (GCATGC), and multiple E-box motifs (CANNTG) and ACGT-core elements, features characteristic of 2S storage protein genes in angiosperms. When fused to the GUS reporter gene, the 1.16 kb Douglas-fir 2S promoter sequence was sufficient to direct transient expression in both developing Douglas-fir embryos and maternally derived haploid megagametophytes. Analysis of this promoter construct in transgenic tobacco showed that expression was restricted to embryo and endosperm in developing seeds and was not detected in vegetative tissues of two-week-old seedlings. These results strongly suggest that both structural and regulatory elements as well as upstream signaling components controlling the expression of 2S albumin genes are highly conserved during evolution.

2S Albumins, Plant↗
PubMed2002

[Mechanisms of antibiotic resistance].

Antibiotics interfere with structural and regulatory elements of bacterial cells leading to growth arrest or cell death. Bacteria have evolved a variety of strategies to overcome the effects of antibiotics. Examples are enzymatic destruction, alteration of the target, efflux and permeability changes. Resistance towards the same substance can be mediated by several mechanisms. Efflux pumps can probably act as mediators of higher resistance development. Alteration of common targets can lead to cross-resistance against several classes of antibiotics. Genetic events, such as point mutations, transfer of plasmids and gen regulation, can mediate a rapid emergence of resistance. Therefore, substances like rifampicin should be only used in combination with other drugs. Accumulation of resistance genes under common regulatory control in integrons induces co-resistance against substances of different specificity. Detailed knowledge of resistance mechanisms, their evolution and dynamics is important for a rational use of antibiotics and other strategies against antibiotic resistance.

Anti-Bacterial Agents↗
PubMed1990

Selector genes and the Cambrian radiation of Bilateria.

There is a significantly greater post-Cambrian decline in frequency of ordinal origination among serially constructed Bilateria, such as arthropods, than in nonserially constructed Bilateria. Greater decline in arthropod ordinal origination is not predicted by ecologic, diversity-dependent models of decline in the production of higher taxa. Reduction in ordinal origination indicates increased constraint on arthropod body-plan evolution. The dispersal of selector genes in the genomes of arthropods in conjunction with the retention of a simple regulatory hierarchy in development may have caused the increased constraint seen. Increased constraint would not be expected in those organisms that are not serially constructed and presumably have not retained the simple ancestral regulatory hierarchy in development of selector gene differentiation of serial elements. The hypothesis of differential constraint tested against the fossil record in this paper can be further tested by examination of the distribution of selector genes in the genomes of arthropods.

Journal Article↗
PubMed2006

Promoter analysis of MADS-box genes in eudicots through phylogenetic footprinting.

The MIKC MADS-box gene family has been shaped by extensive gene duplications giving rise to subfamilies of genes with distinct functions and expression patterns. However, within these subfamilies the functional assignment is not that clear-cut, and considerable functional redundancy exists. One way to investigate the diversity in regulation present in these subfamilies is promoter sequence analysis. With the advent of genome sequencing projects, we are now able to exert a comparative analysis of Arabidopsis and poplar promoters of MADS-box genes belonging to the same subfamily. Based on the principle of phylogenetic footprinting, sequences conserved between the promoters of homologous genes are thought to be functional. Here, we have investigated the evolution of MADS-box genes at the promoter level and show that many genes have diverged in their regulatory sequences after duplication and/or speciation. Furthermore, using phylogenetic footprinting, a distinction can be made between redundancy, neo/nonfunctionalization, and subfunctionalization.

Arabidopsis↗
PubMed2002

The Opitz syndrome gene Mid1 is transcribed from a human endogenous retroviral promoter.

Human endogenous retroviruses (HERVs) and other long terminal repeat (LTR)-containing elements comprise a significant portion (8%) of the human genome and are likely vestiges of retroviral infections during primate evolution. Many of the HERVs present in human DNA have retained functional promoter, enhancer, and polyadenylation signals, and these regulatory sequences have the potential to modify the expression of nearby genes. To identify retroviral elements that contribute to the transcription of human genes, we screened sequence databases for chimeric (viral-cellular) transcripts. These searches revealed a fusion transcript containing the LTR of an HERV-E element linked to the Opitz syndrome gene Mid1. We confirmed the authenticity of the chimeric transcript by 5' rapid amplification of cDNA ends (RACE) and established that the Mid1 mRNA isoform was transcribed from a retroviral LTR. The identification of a retroviral first exon suggested the existence of alternative promoters for Mid1 because nonretroviral (native) 5' untranslated regions (UTRs) had been reported previously for this gene. Although Mid1 transcripts could be detected in all tissues tested, quantitative real-time reverse transcription-polymerase chain reaction indicated that the retroviral promoter contributes significantly to the level of Mid1 transcripts in placenta and embryonic kidney, where chimeric mRNAs were found to represent 25% and 22% of overall Mid1 mRNAs, respectively. Transient transfection studies supported a role for the LTR as a strong tissue-specific promoter in placental and embryonic kidney cell lines and suggested a function for the LTR as an enhancer. These findings provide further evidence that some endogenous retroviruses have evolved a biological function by contributing transcriptional regulatory elements to cellular genes.

Base Sequence↗
PubMed2025

Activation and modulation of the host response to DNA damage by an integrative and conjugative element.

Mobile genetic elements help drive horizontal gene transfer and bacterial evolution. Conjugative elements and temperate bacteriophages can be stably maintained in host cells. They can alter host physiology and regulatory responses and typically carry genes that are beneficial to their hosts. We found that ICEBs1, an integrative and conjugative element (ICE) of Bacillus subtilis, inhibits the host response to DNA damage (the SOS response). Activation of ICEBs1 before DNA damage reduced host cell lysis that was caused by SOS-mediated activation of two resident prophages. Further, activation of ICEBs1 itself activated the SOS response in a subpopulation of cells, and this activation was attenuated by the functions of the ICEBs1 genes ydcT and yddA (now ramT and ramA; ram for RecA modulator). Double-mutant analyses indicated that RamA functions to inhibit and RamT functions to both inhibit and activate the SOS response. Both RamT and RamA caused a reduction in RecA filaments, one of the early steps in activation of the SOS response. We suspect that there are several different mechanisms by which mobile genetic elements that generate single-stranded DNA (ssDNA) during their life cycle inhibit the host SOS response and RecA function, as RamT and RamA differ from the known SOS inhibitors encoded by conjugative elements.IMPORTANCEBacterial genomes typically contain mobile genetic elements, including bacteriophages (viruses) and integrative and conjugative elements, that affect host physiology. ICEs can excise from the chromosome and undergo rolling-circle replication, producing ssDNA, a signal that indicates DNA damage and activates the host SOS response. We found that following excision and replication, ICEBs1 of B. subtilis stimulates the host SOS response and that ICEBs1 encodes two proteins that limit the extent of this response. These proteins also reduce the amount of cell killing caused by resident prophages following their activation by DNA damage. These proteins are different from those previously characterized that inhibit the host SOS response and represent a new way in which ICEs can affect their host cells.

Bacillus subtilis↗
PubMed2004

The genetics and properties of cereal ribosome-inactivating proteins.

Plants contain proteins that are capable of inactivating ribosomes, commonly referred to as Ribosome Inactivating Proteins (RIPs). These particular plant proteins have received attention in biological and biomedical research because of their unique biological activities towards animals and human cells as cell-killing agents. Some of the best-characterised RIPs have been isolated from exotic plants, but they have also been found in cereals and other food crops. Cereals contain, in general, RIPs in the endosperm protein pool: they share a high similarity with all the other RIPs retaining, however, characteristic features forming a distinct class which diversified significantly during evolution. They appear to be involved in quite different physiological roles, such as defence against pathogens and/or involved in regulatory and developmental processes. This review aims to provide a critical assessment to work related to cereal RIP with particular emphasis to the maize RIPs.

Edible Grain↗
PubMedDate not supplied

[Pharmacy in the 90's: the modern process of drug registration].

The 5 phases of the development of a drug are reviewed in the light of the modern scientific guide-lines. The needed documentation (master-file) and technical-scientific data are (and will be) constantly more demanding. Therefore, the drugs will undergo a hard selection. The Regulations for Marketing Authorizations, already of a high regulatory level, are increasingly in agreement. Therefore, the gap existing in the past among countries with a different technological evolution is filled. The measures of the Health Authorities before and after the authorization to the marketing of the medicinal specialties are always more systematic. Many procedures clearly pointing out the process of the study of a substances destined to become a drug (GMP - GLP - GCP - DMF) are now established on an international level. The drugs of the nineties will undergo a very hard selection, to warrant a positive risk-benefit balance and a profitable cost-benefit ratio. The compound under study are numbered in hundreds, whereas those which pass the screening and can be used as specialties are very few. The costs of development can be estimated in tens of billion liras and the times required on average are of about 10 years for each project. The attention of the scientists and the pharmaceutical companies is directed especially to the development of innovative drugs for the treatment of the most important diseases.

Drug Design↗
PubMed1984

A cytosolic cyclic AMP-dependent protein kinase in Dictyostelium discoideum. I. Properties.

A cAMP-dependent protein kinase was isolated and partially purified from Dictyostelium discoideum. The cytosolic holoenzyme has an apparent Mr = 160,000-180,000; its activity was stimulated significantly by cAMP when Kemptide served as substrate. The enzyme was dissociated and the regulatory subunit purified by affinity chromatography on 8-aminoethylamino-cAMP. Only one type of regulatory subunit was found; it has an apparent Mr = 41,000 and is a substrate for the in vitro phosphorylation by the homologous catalytic subunit and by purified bovine catalytic subunit. Antibody against the regulatory subunit was prepared. The D. discoideum catalytic subunit was separated from cAMP-independent protein kinase by chromatofocusing. The apparent molecular weight of the catalytic subunit of the D. discoideum cAMP-dependent protein kinase is 33,000 and its pI is 6.4. The enzyme catalyzed the phosphorylation of bovine RII but not of RI regulatory subunit and was inhibited by high concentrations of the inhibitor of mammalian cAMP-dependent protein kinase. The evolution of the functional domains of cAMP-dependent protein kinases is discussed on the basis of a comparison of the analogous D. discoideum and vertebrate enzymes.

Animals↗
PubMed1991

Evidence for three genes encoding class-I alcohol dehydrogenase subunits in baboon and analysis of the 5' region of the gene encoding the ADH beta subunit.

Five alcohol dehydrogenases (ADH; alcohol: NAD+ oxidoreductase; EC 1.1.1.1) have been identified in the baboon. All are homodimers of five distinct ADH subunits, with the two class-I ADH subunits being differentially expressed in the liver (the beta-subunit) and kidney. We have hybridized restriction-enzyme-digested baboon DNA to a 30-bp probe or a 337-bp DNA fragment, to reveal the presence of three genes encoding class-I ADH subunits in the baboon genome. This result was confirmed by the amplification of three different baboon ADH (bADH) nucleotide (nt) sequences, corresponding to exon 5 in the human gene encoding ADH beta (hADHB) from baboon DNA. Two of these sequences are identical to previously isolated liver and kidney cDNA nt sequences. These results are consistent with a phylogenetic analysis of the nt sequences of class-I hADH and bADH genes. Then, using primers based on the nt sequence of hADHB, we amplified a 336-bp DNA fragment, from genomic DNA, encoding the 5' region of the bADHB gene. In a 49-bp region of overlap, the nt sequence of this DNA fragment was identical to the sequence of a cDNA fragment amplified from baboon liver mRNA, whereas there were seven differences between this DNA fragment and the sequence of a cDNA amplified from baboon kidney mRNA. We used primer extension analysis to identify three adjacent transcriptional start points (tsp) for bADHB mRNA. Initiation of transcription at the most 5' bp leaves a 72-bp untranslated region. Examination of the sequence upstream from the tsp reveals a number of conserved putative regulatory sequence elements.

Alcohol Dehydrogenase↗
PubMed2004

Conserved and acquired features of neurogenin1 regulation.

The telencephalon shows vast morphological variations among different vertebrate groups. The transcription factor neurogenin1 (ngn1) controls neurogenesis in the mouse pallium and is also expressed in the dorsal telencephalon of the evolutionary distant zebrafish. The upstream regions of the zebrafish and mammalian ngn1 loci harbour several stretches of conserved sequences. Here, we show that the upstream region of zebrafish ngn1 is capable of faithfully recapitulating endogenous expression in the zebrafish and mouse telencephalon. A single conserved regulatory region is essential for dorsal telencephalic expression in the zebrafish, and for expression in the dorsal pallium of the mouse. However, a second conserved region that is inactive in the fish telencephalon is necessary for expression in the lateral pallium of mouse embryos. This regulatory region, which drives expression in the zebrafish diencephalon and hindbrain, is dependent on Pax6 activity and binds recombinant Pax6 in vitro. Thus, the regulatory elements of ngn1 appear to be conserved among vertebrates, with certain differences being incorporated in the utilisation of these enhancers, for the acquisition of more advanced features in amniotes. Our data provide evidence for the co-option of regulatory regions as a mechanism of evolutionary diversification of expression patterns, and suggest that an alteration in Pax6 expression was crucial in neocortex evolution.

Amino Acid Sequence↗
PubMed1991

Structure and molecular evolutionary analysis of a plant cytochrome c gene: surprising implications for Arabidopsis thaliana.

We have isolated a cytochrome c gene from Arabidopsis thaliana (cv. Columbia), which is the first cytochrome c gene to be cloned from a higher plant. Genomic DNA blot analysis indicates that there is only one copy of cytochrome c in Arabidopsis. The gene consists of three exons separated by two introns. Gene features such as regulatory regions, codon usage, and conserved splicing-specific sequences are all present and typical of dicotyledonous plant nuclear genes. We have constructed phenograms and cladograms for cytochrome c amino acid sequences and histone H3, alcohol dehydrogenase, and actin DNA sequences. For both cytochrome c and histone H3, Arabidopsis clusters poorly with other higher plants. Instead, it clusters with Neurospora and/or the yeasts. We suggest that perhaps this observation should be considered when using Arabidopsis as a model system for higher plants.

Actins↗
PubMed1988

The structure of the regulatory region of the rat L1 (L1Rn, long interspersed repeated) DNA family of transposable elements.

Here we report the DNA structure of the left 1.5 kb of two newly isolated full length members of the rat L1 DNA family (L1Rn, long interspersed repeated DNA). In contrast to earlier isolated rat L1 members, both of these contain promoter-like regions that are most likely full length. In addition, the promoter-like region of both members has undergone a partial tandem duplication. A second internal region of the left end of one of the reported members is also tandemly duplicated. The propensity of the left end of rat L1 elements to undergo this form of genetic rearrangement, as well as other structural features revealed by the present work, is discussed in light of the fact that during evolution the otherwise conserved mammalian L1 DNA families have each acquired completely different promoter-like regions. In an accompanying paper [Nur, I., Pascale, E., and Furano, A. V. (1988) Nucleic Acids Res. 16, submitted], we report that one of the rat promoter-like regions can function as a promoter in rat cells when fused to the Escherichia coli chloramphenicol acyltransferase gene.

Amino Acid Sequence↗
PubMed1990

Molecular analysis of an alcohol dehydrogenase-encoding genomic clone (adh2) from rice.

An alcohol dehydrogenase-encoding gene was isolated from a rice genomic library. The coding region was sequenced, and the gene was identified as adh2. The nucleotide sequence of this gene contains an open reading frame which is interrupted by nine introns. Sequences that are important for eukaryotic gene expression, e.g. the TATA box, polyadenylation signal, intron/exon junction and putative splicing branch sites, are found in the expected locations in the rice adh2. A sequence related to the hexanucleotide core of regulatory elements identified in anaerobically induced plant genes is also present in the 5' region of the rice adh2.

Alcohol Dehydrogenase↗