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The Journal of Biological Chemistry Jul 1994The cell-surface glycoprotein CD36 interacts with a large variety of ligands, including collagen types I and IV, thrombospondin, erythrocytes parasitized with Plasmodium...
The cell-surface glycoprotein CD36 interacts with a large variety of ligands, including collagen types I and IV, thrombospondin, erythrocytes parasitized with Plasmodium falciparum, platelet-agglutinating protein p37, oxidized low density lipoprotein, and long-chain fatty acids. Its expression is restricted to platelets, monocytes, adipocytes, and some endothelial and epithelial cells and is regulated during cell activation, differentiation, and development. CD36 belongs to a novel gene family of structurally related glycoproteins that includes CLA-1 and the lysosomal membrane glycoprotein LIMPII. To advance our knowledge on the genomic organization and the regulation of the cellular expression of the genes of this family, we have investigated the structural organization of the human CD36 gene and of its 5'-proximal flanking region. The CD36 gene is encoded by 15 exons that extend more than 32 kilobases on the human genome. Interestingly, the CD36 mRNA 5'-untranslated region is encoded by three exons. The 3'-untranslated region is contained in two exons, whose expression pattern can originate two mRNA forms. The cytoplasmic and transmembrane regions predicted at both terminal ends of the polypeptide chain are encoded by single exons, while the extracellular domain is encoded by 11 exons. The transcription initiation site of the CD36 gene is located 289 nucleotides upstream from the translational start codon. Sequence analysis of the proximal 5'-flanking region of the gene reveals the existence of a TATA box appropriately located with respect to the transcription initiation site and several potential cis-regulatory elements that might contribute to the transcriptional regulation of the CD36 gene. Delineation of the structural organization of the CD36 gene may help in defining the boundaries of relevant structural and/or functional domains in CD36 and, by extension, in the other members of the family.
Topics: Antigens, CD; Base Sequence; CD36 Antigens; Exons; Genes; Humans; Molecular Sequence Data; Oligodeoxyribonucleotides; Promoter Regions, Genetic; RNA, Messenger; Restriction Mapping; Transcription, Genetic
PubMed: 7518447
DOI: No ID Found -
American Journal of Respiratory Cell... Sep 1989Collagens are extracellular matrix proteins that play important structural roles in many tissues and organs. Thirteen types of collagen, the products of 23 genes, have... (Review)
Review
Collagens are extracellular matrix proteins that play important structural roles in many tissues and organs. Thirteen types of collagen, the products of 23 genes, have been described. Most of the collagen genes are developmentally regulated; a given tissue or cell type expresses only a subset of the collagen genes. Type I collagen, the most abundant protein in vertebrate connective tissues, is produced by most cells of mesenchymal origin except hyaline cartilage. Each tissue or cell type expresses the type I collagen genes at a characteristic rate. Maintenance of the normal synthetic rate appears to be important for preservation of normal tissue structure and function. Fibrotic lesions are characterized by increased production of type I collagen. The mechanisms that determine both the normal tissue-specific pattern of type I collagen gene expression and the elevated expression in fibrosis are complex. Both transcriptional and post-transcriptional mechanisms have been described, with modulation of mRNA stability being perhaps the most important post-transcriptional mechanism. Several sequences have been identified in the promoters of the type I collagen genes which are required for transcriptional activity; in addition, transcriptional enhances have been identified within the first introns of the genes. Type I collagen gene expression is also regulated both positively and negatively by a variety of exogenous factors, including inflammatory response mediators. The specific combination of such exogenous factors available in a given tissue probably determines the net rate at which the genes are expressed.
Topics: Collagen; Enhancer Elements, Genetic; Fibrosis; Gene Expression Regulation; Genes; Promoter Regions, Genetic; RNA, Messenger; Regulatory Sequences, Nucleic Acid
PubMed: 2696511
DOI: 10.1165/ajrcmb/1.3.161 -
Genomics Apr 1993Glutamate dehydrogenase is a mitochondrially located, key metabolic enzyme. In addition to its general metabolic role, GLUD is important in neurotransmission....
Glutamate dehydrogenase is a mitochondrially located, key metabolic enzyme. In addition to its general metabolic role, GLUD is important in neurotransmission. Significant alterations in GLUD enzymatic activity have been associated with certain neurodegenerative human disorders. Although a single species of human GLUD cDNA molecule has been identified so far, both genomic DNA Southern and cytogenetic analyses have indicated the presence of a GLUD gene family. Screening of a human genomic lambda-phage library with the GLUD cDNA, led us to the isolation of several clones divided into five structurally distinct contigs. We have confirmed the presence of all GLUD-specific sequences in the human genome by detailed genomic Southern analysis. This study allowed the identification of the entire functional GLUD gene, named GLUD1. The GLUD1 gene is about 45 kb long and it is organized into 13 exons. Its nucleotide sequence, exon-intron boundaries, and transcription start sites were determined. Potential binding sites for various regulatory factors such as Sp1, AP-1, and AP-2 were recognized at the promoter region of the gene. The members of the other contigs showed an organization clearly different from GLUD1. Two distinct GLUD-specific gene loci, termed GLUDP2 and GLUDP3, possibly represent truncated pseudogenes. Their high degree of similarity to GLUD1 is limited to the region surrounding exons 2, 3, and 4. Finally, two additional GLUD-specific genomic sequences, termed GLUDP4 and GLUDP5, are structurally similar with the 3' part of the GLUD cDNA sequence. These loci probably represent truncated GLUD pseudogenes generated by retrotransposition. The data presented here suggest that all human GLUD pseudogenes have diverged recently in evolution.
Topics: Amino Acid Sequence; Base Sequence; Chromosome Mapping; Cloning, Molecular; DNA; Exons; Genes, Regulator; Glutamate Dehydrogenase; Humans; Introns; Molecular Sequence Data; Multigene Family; Nucleic Acid Hybridization; Transcription, Genetic
PubMed: 8486350
DOI: 10.1006/geno.1993.1152 -
Antonie Van Leeuwenhoek Feb 1996Lantibiotics form a group of modified peptides with unique structures, containing post-translationally modified amino acids such as dehydrated and lanthionine residues.... (Comparative Study)
Comparative Study Review
Lantibiotics form a group of modified peptides with unique structures, containing post-translationally modified amino acids such as dehydrated and lanthionine residues. In the gram-positive bacteria that secrete these lantibiotics, the gene clusters flanking the structural genes for various linear (type A) lantibiotics have recently been characterized. The best studied representatives are those of nisin (nis), subtilin (spa), epidermin (epi), Pep5 (pep), cytolysin (cyl), lactocin S (las) and lacticin 481 (lct). Comparison of the lantibiotic gene clusters shows that they contain conserved genes that probably encode similar functions. The nis, spa, epi and pep clusters contain lanB and lanC genes that are presumed to code for two types of enzymes that have been implicated in the modification reactions characteristic of all lantibiotics, i.e. dehydration and thio-ether ring formation. The cyl, las and lct gene clusters have no homologue of the lanB gene, but they do contain a much larger lanM gene that is the lanC gene homologue. Most lantibiotic gene clusters contain a lanP gene encoding a serine protease that is presumably involved in the proteolytic processing of the prelantibiotics. All clusters contain a lanT gene encoding an ABC transporter likely to be involved in the export of (precursors of) the lantibiotics. The lanE, lanF and lanG genes in the nis, spa and epi clusters encode another transport system that is possibly involved in self-protection. In the nisin and subtilin gene clusters two tandem genes, lanR and lanK, have been located that code for a two-component regulatory system. Finally, non-homologous genes are found in some lantibiotic gene clusters. The nisI and spaI genes encode lipoproteins that are involved in immunity, the pepI gene encodes a membrane-located immunity protein, and epiD encodes an enzyme involved in a post-translational modification found only in the C-terminus of epidermin. Several genes of unknown function are also found in the las gene cluster. A database has been assembled for all putative gene products of type A lantibiotic gene clusters. Database searches, multiple sequence alignment and secondary structure prediction have been used to identify conserved sequence segments in the LanB, LanC, LanE, LanF, LanG, LanK, LanM, LanP, LanR and LanT gene products that may be essential for structure and function. This database allows for a rapid screening of newly determined sequences in lantibiotic gene clusters.
Topics: ATP-Binding Cassette Transporters; Amino Acid Sequence; Anti-Bacterial Agents; Bacterial Proteins; Gene Expression Regulation, Bacterial; Genes, Bacterial; Molecular Sequence Data; Multigene Family; Operon; Protein Biosynthesis; Protein Processing, Post-Translational; Protein Sorting Signals; Sequence Homology, Amino Acid
PubMed: 8775977
DOI: 10.1007/BF00399422 -
Philosophical Transactions of the Royal... Dec 1999Protein crystallography has become a major technique for understanding cellular processes. This has come about through great advances in the technology of data... (Review)
Review
Protein crystallography has become a major technique for understanding cellular processes. This has come about through great advances in the technology of data collection and interpretation, particularly the use of synchrotron radiation. The ability to express eukaryotic genes in Escherichia coli is also important. Analysis of known structures shows that all proteins are built from about 1000 primeval folds. The collection of all primeval folds provides a basis for predicting structure from sequence. At present about 450 are known. Of the presently sequenced genomes only a fraction can be related to known proteins on the basis of sequence alone. Attempts are being made to determine all (or as many as possible) of the structures from some bacterial genomes in the expectation that structure will point to function more reliably than does sequence. Membrane proteins present a special problem. The next 20 years may see the experimental determination of another 40,000 protein structures. This will make considerable demands on synchrotron sources and will require many more biochemists than are currently available. The availability of massive structure databases will alter the way biochemistry is done.
Topics: Crystallography, X-Ray; Gene Expression Regulation, Bacterial; Genes; Magnetic Resonance Spectroscopy; Microscopy, Electron; Molecular Biology; Protein Folding; Synchrotrons
PubMed: 10670018
DOI: 10.1098/rstb.1999.0537 -
Trends in Genetics : TIG Mar 2013Many bacterial and archaeal lineages have a history of extensive and ongoing horizontal gene transfer and loss, as evidenced by the large differences in genome content... (Review)
Review
Many bacterial and archaeal lineages have a history of extensive and ongoing horizontal gene transfer and loss, as evidenced by the large differences in genome content even among otherwise closely related isolates. How ecologically cohesive populations might evolve and be maintained under such conditions of rapid gene turnover has remained controversial. Here we synthesize recent literature demonstrating the importance of habitat and niche in structuring horizontal gene transfer. This leads to a model of ecological speciation via gradual genetic isolation triggered by differential habitat-association of nascent populations. Further, we hypothesize that subpopulations can evolve through local gene-exchange networks by tapping into a gene pool that is adaptive towards local, continuously changing organismic interactions and is, to a large degree, responsible for the observed rapid gene turnover. Overall, these insights help to explain how bacteria and archaea form populations that display both ecological cohesion and high genomic diversity.
Topics: Archaea; Bacteria; Ecosystem; Evolution, Molecular; Gene Transfer, Horizontal; Genes, Bacterial; Genotype; Multigene Family
PubMed: 23332119
DOI: 10.1016/j.tig.2012.12.006 -
Planta Medica Oct 2006Plants and microorganisms are the most important sources of secondary metabolites in nature. For research in the functional genomics of secondary metabolism, and for the... (Review)
Review
Plants and microorganisms are the most important sources of secondary metabolites in nature. For research in the functional genomics of secondary metabolism, and for the biotechnological application of such research by genetic engineering and combinatorial biosynthesis, most microorganisms offer a unique advantage to the researcher: the biosynthetic genes for a specific secondary metabolite are not scattered over the genome, but rather are clustered in a well-defined, contiguous region - the biosynthetic gene cluster of that metabolite. This is exemplified in this review for the biosynthetic gene clusters of the aminocoumarin antibiotics novobiocin, clorobiocin and coumermycin A (1), which are potent inhibitors of DNA gyrase. Cloning, sequencing and analysis of the biosynthetic gene clusters of these three antibiotics revealed that the structural differences and similarities of the compounds are perfectly reflected by the genetic organisation of the biosynthetic gene clusters. The function of most biosynthetic genes could be identified by gene inactivation experiments as well as by heterologous expression and biochemical investigation. The prenylated benzoic acid moiety of novobiocin and clorobiocin, involved in the interaction with gyrase, is structurally similar to metabolites found in plants. However, detailed investigations of the biosynthesis revealed that the biosynthetic pathway and the enzymes involved are totally different from those identified in plants.
Topics: Aminocoumarins; Genes, Bacterial; Molecular Structure; Multigene Family; Novobiocin; Streptomyces
PubMed: 16868863
DOI: 10.1055/s-2006-946699 -
Plant Physiology May 2014The structure of eukaryotic genes evolves extensively by intron loss or gain. Previous studies have revealed two models for gene structure evolution through the loss of...
The structure of eukaryotic genes evolves extensively by intron loss or gain. Previous studies have revealed two models for gene structure evolution through the loss of introns: RNA-based gene conversion, dubbed the Fink model and retroposition model. However, retrogenes that experienced both intron loss and intron-retaining events have been ignored; evolutionary processes responsible for the variation in complex exon-intron structure were unknown. We detected hundreds of retroduplication-derived genes in human (Homo sapiens), fly (Drosophila melanogaster), rice (Oryza sativa), and Arabidopsis (Arabidopsis thaliana) and categorized them either as duplicated genes that have all introns lost or as duplicated genes that have at least lost one and retained one intron compared with the parental copy (intron-retaining [IR] type). Our new model attributes intron retention alternative splicing to the generation of these IR-type gene pairs. We presented 25 parental genes that have an intron retention isoform and have retained introns in the same locations in the IR-type duplicate genes, which directly support our hypothesis. Our alternative-splicing-based model in conjunction with the retroposition and Fink models can explain the IR-type gene observed. We discovered a greater percentage of IR-type genes in plants than in animals, which may be due to the abundance of intron retention cases in plants. Given the prevalence of intron retention in plants, this new model gives a support that plant genomes have very complex gene structures.
Topics: Alternative Splicing; Animals; Arabidopsis; Evolution, Molecular; Gene Conversion; Gene Duplication; Genes, Duplicate; Genes, Plant; Humans; Introns; Models, Genetic; Oryza; Protein Isoforms; Retroelements
PubMed: 24520158
DOI: 10.1104/pp.113.231696 -
PloS One 2022Despite its high and direct impact on nearly all biological processes, the underlying structure of gene-gene interaction networks is investigated so far according to...
Despite its high and direct impact on nearly all biological processes, the underlying structure of gene-gene interaction networks is investigated so far according to pair connections. To address this, we explore the gene interaction networks of the yeast Saccharomyces cerevisiae beyond pairwise interaction using the structural balance theory (SBT). Specifically, we ask whether essential and nonessential gene interaction networks are structurally balanced. We study triadic interactions in the weighted signed undirected gene networks and observe that balanced and unbalanced triads are over and underrepresented in both networks, thus beautifully in line with the strong notion of balance. Moreover, we note that the energy distribution of triads is significantly different in both essential and nonessential networks compared to the shuffled networks. Yet, this difference is greater in the essential network regarding the frequency as well as the energy of triads. Additionally, results demonstrate that triads in the essential gene network are more interconnected through sharing common links, while in the nonessential network they tend to be isolated. Last but not least, we investigate the contribution of all-length signed walks and its impact on the degree of balance. Our findings reveal that interestingly when considering longer cycles, not only, both essential and nonessential gene networks are more balanced compared to their corresponding shuffled networks, but also, the nonessential gene network is more balanced compared to the essential network.
Topics: Gene Regulatory Networks; Genes, Essential; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 35353818
DOI: 10.1371/journal.pone.0258596 -
Journal of Cellular Biochemistry Oct 1991It is hypothesized that nuclear DNA is organized in topologically constrained loop domains defining basic units of higher order chromatin structure. Our studies are... (Review)
Review
It is hypothesized that nuclear DNA is organized in topologically constrained loop domains defining basic units of higher order chromatin structure. Our studies are performed in order to investigate the functional relevance of this structural subdivision of eukaryotic chromatin for the control of gene expression. We used the chicken lysozyme gene locus as a model to examine the relation between chromatin structure and gene function. Several structural features of the lysozyme locus are known: the extension of the region of general DNAasel sensitivity of the active gene, the location of DNA-sequences with high affinity for the nuclear matrix in vitro, and the position of DNAasel hypersensitive chromatin sites (DHSs). The pattern of DHSs changes depending on the transcriptional status of the gene. Functional studies demonstrated that DHSs mark the position of cis-acting regulatory elements. Additionally, we discovered a novel cis-activity of the border regions of the DNAasel sensitive domain (A-elements). By eliminating the position effect on gene expression usually observed when genes are randomly integrated into the genome after transfection, A-elements possibly serve as punctuation marks for a regulatory chromatin domain. Experiments using transgenic mice confirmed that the complete structurally defined lysozyme gene domain behaves as an independent regulatory unit, expressing the gene in a tissue specific and position independent manner. These expression features were lost in transgenic mice carrying a construct, in which the A-elements as well as an upstream enhancer region were deleted, indicating the lack of a locus activation function on this construct. Experiments are designed in order to uncover possible hierarchical relationships between the different cis-acting regulatory elements for stepwise gene activation during cell differentiation. We are aiming at the definition of the basic structural and functional requirements for position independent and high level gene expression. The result of these experiments will have important consequences for random gene transfer with predictable and reproducible expression of transgenes.
Topics: Animals; Chickens; Chromatin; Chromosome Mapping; Deoxyribonuclease I; Genes, Regulator; Muramidase; Transfection
PubMed: 1757483
DOI: 10.1002/jcb.240470203