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Showing papers on "Gene expression published in 1968"



Journal ArticleDOI
26 Oct 1968-Nature
TL;DR: The use of a novel protein fingerprinting technique has shown that, in a cell-free system, the three genes of bacteriophage f2 can be translated independently.
Abstract: The use of a novel protein fingerprinting technique has shown that, in a cell-free system, the three genes of bacteriophage f2 can be translated independently. A crude genetic map of f2 RNA was constructed by using specific fragments of f2 RNA as messenger.

134 citations


Journal ArticleDOI
TL;DR: Genetic evidence for a mammalian gene that appears to control the expression of an independent structural gene in a differentiated cell is presented, and developmental specificity of such tissue indicates that control mechanisms exist for regulating the relative amounts of synthesis of the A and B subunits of LDH.
Abstract: Experimental evidence suggests that cells comprising complex multicellular organisms possess qualitatively equivalent ensembles of genes, but the differentiation of these cells requires differential gene expression. According to this hypothesis, differentiation occurs primarily as the result of a patterned activation of certain genes and a repression of others. Developmental control of gene expression can operate at many levels, such as transcription, translation, end product alteration, or combinations of these. It is reasonable to expect that the control processes should themselves be genetically controlled and, as a result, that mutations affecting control should also occur. Evidence for mutations affecting certain levels of control in higher organisms exists in fungi, Drosophila, plants, and mammals.'-3 These examples provide some insight into the mechanisms controlling differential gene expression. In this report we present genetic evidence for a mammalian gene that appears to control the expression of an independent structural gene in a differentiated cell. This gene controls the appearance of the active B subunit, but not the A subunit, of the lactate dehydrogenase (LDH) tetramer in mouse erythrocytes. It has no detectable effect in any other tissue examined. Preliminary evidence has been reported elsewhere.4 Lactate dehydrogeniase (EC 1.1.1.27) is composed of two electrophoretically distinct subunits, A and B, which associate at random to form five tetrameric isozymes, each with a molecular weight of about 135,000.5, 6 The five isozymes are generated by assortment of the A and B subunits into all possible combinations of four.7 Formulas for the five isozymes may be written as follows: BBBB = LDH-1; BBBA = LDH-2; BBAA = LDH-3; BAAA = LDH-4; AAAA = LDH-5. These five forms are the principal lactate dehydrogenase isozymes found ubiquitously in mammals. A high degree of tissue specificity characterizes isozyme patterns. Certain tissues contain more LDH-5 than LDH-1, thus demonstrating that unequal amounts of the A and B subunits are available for tetrameric association. Differential expression of the LDH isozymes has also been shown during specific tissue development.8 The developmental specificity of such tissue indicates that control mechanisms exist for regulating the relative amounts of synthesis of the A and B subunits of LDH. In the present study two lactate dehydrogenase phenotypes were observed in mouse erythrocytes but not in other tissues. In one phenotype, LDH B subunits were expressed, while in the second, LDH B subunits were absent. This phenotypic difference was iniherited according to expectations of two alleles at an autosomal locus. The allele that specifies the formation of LIDH B subunits is dominant to that which is associated with the absence of these subunits.

86 citations


Book ChapterDOI
TL;DR: Evidence has been provided to support the concept that cell division is a prerequisite for the expression of new differentiated function, and the requirement for cell division and the basis for the new genetic expression remain to be explained in molecular terms.
Abstract: Publisher Summary This chapter discusses the studies of the synthesis of specific protein markers of differentiated function in an attempt to define stages of transition in the differentiation of mammary alveolar cells in vitro. These studies have provided information relating to several major questions regarding the nature of differentiation of mammalian cells. Evidence has been provided to support the concept that cell division is a prerequisite for the expression of new differentiated function. The agent of primary importance in effecting covert differentiation, hydrocortisone, acts upon the parent cells, and new function is expressed by the daughter cells. However, the requirement for cell division and the basis for the new genetic expression remain to be explained in molecular terms. Concern with the intracellular control mechanisms involved must be coupled with recognition of the possible importance of mesenchymal cells in modifying the response of epithelial cells. These studies have emphasized the vulnerability of proliferating cells to factors in the environment, especially to hormonal agents that have the capacity to alter genetic expression within cells.

46 citations


Journal ArticleDOI
29 Jun 1968-Nature
TL;DR: Using hybridization techniques, the emergence of new mRNA species has been reported during amphibian and sea urchin development, and it seems plausible that new mRNA also appears during embryonic differentiation.
Abstract: THE molecular control mechanisms regulating embryogenesis are not fully defined. The appearance of morphological differentiation must reflect prior biochemical differentiation and changes in patterns of protein synthesis. In spite of the well documented evidence that mRNA is present before the eggs are fertilized1, it seems plausible that new mRNA also appears during embryonic differentiation. Adult tissue-specific proteins may then be synthesized in response to the appearance of these new chemical signals. Using hybridization techniques, the emergence of new mRNA species has been reported during amphibian2 and sea urchin3 development.

37 citations



Journal ArticleDOI
TL;DR: The multiplication in Escherichia coli of both DNA and RNA bacteriophages was found to be inhibited by the antibiotic phleomycin, which inhibited the synthesis of bacterial RNA, and secondarily, of bacterial protein in E. coli.

15 citations


Journal ArticleDOI
01 Aug 1968-Genetics
TL;DR: The possibility that the effects of rec genes on recombination frequency may reflect modifications of an integrated, dual purpose, control system acting at the gene level is considered.
Abstract: ENES affecting the frequency of recombination between allelic differences have been found in Neurospora crassa (JESSOP and D. G. CATCHESIDE 1965; D. G. CATCHESIDE 1966; JHA 1967). In the two most extensively studied cases, crosses homozygous for rec (a general symbol for genes affecting recombination) exhibit allelic recombination frequencies an order of magnitude or more greater than those containing the recf allele. The rec genes are specific, rec-2 affecting recombination frequency between his2 (histidine-2) alleles and rec-3 that between am-l (amination-l) alleles. There is no interaction between rec-2 and am-1 nor between rec-3 and his-2 (D. G. CATCHESIDE 1966). Neither rec gene is contiguous with the structural gene which it affects. Indeed, rec-3 is located about 12 map units proximal to mating type in linkage group I whilst am-1 is in linkage group V and rec-2 is about 19 units distal to his-2 also in linkage group V (D. G. CATCHESIDE 1966 and unpublished observations). The dominant nature, specificity and remoteness of the recf genes from their points of action has led to the proposition that they are regulatory genes (D. G. CATCHESIDE 1966; WHtTEHousE 1966) analogous to those described in other organisms (MCCLINTOCK 1957; JACOB and MONOD 1961). Regulation by rec+ is most simply envisaged as acting directly at the gene level by the agency of a gene product which prevents either the formation of hybrid DNA or the correction of any consequently mispaired bases. The polarized effect of rec on either or both of these processes (D. G. CATCHESIDE 1967) is most simply described in terms of a direct control at the gene level (D. E. A. CATCHESIDE 1967). This paper considers the possibility that the effects of rec genes on recombination frequency may reflect modifications of an integrated, dual purpose, control system acting at the gene level; D. G. CATCHESIDE (1966) and WHITEHOUSE (1966) have suggested lbat control of recombination and transcription may be integrated. The rec-3, an-2 pair has been chosen for investigation as it has a number of convenient properties. Mutants at the am-1 locus are known to produce nicotine adenine dinucleotide phosphate-specific glutamate dehydrogenase (NADP-GDH; Enzyme Commission number 1.4.1.4) varieties which differ in properties from the wild-type enzyme (FINCHAM 1962:; FINCHAM and STADLER 1965). Hence, the am-2 locus

12 citations


Journal ArticleDOI
TL;DR: The isolated thymus nucleus is shown to synthesize RNA similar to that found in the nucleus and in the cytoplasm, and the intracellular distribution of RNA species was investigated and differences were found between nuclear RNA and cy toplasmic RNA.
Abstract: In vitro synthesis of RNA by nuclei isolated from various tissues has been observed in many laboratories (1-3). Several investigators have realized the usefulness of isolated nuclei for studying the regulation of RNA synthesis. The effects of nuclear proteins (4) and various hormones, (5-7) for example, on the incorporation of various precursors into RNA have been analyzed recently. However, if the full potential of isolated nuclei as an assay system for studying the regulation of RNA synthesis is to be realized, then it is necessary that the characterization of the synthesized RNA be more complete. In the present studies, we have used the technique of DNA-RNA hybridization in an attempt to characterize the RNA synthesized in vitro by thymus nuclei. We have shown that the isolated thymus nucleus is capable of synthesizing a population of RNA molecules that is specific to thymus. The intracellular distribution of RNA species was also investigated and differences were found between nuclear RNA and cytoplasmic RNA. The isolated nucleus was shown to synthesize RNA similar to that found in the nucleus and in the cytoplasm.

12 citations



Journal ArticleDOI
TL;DR: Evidence stems from the induction of puffs in giant chromosomes by the insect hormone ecdysone, the stimulation of nucleic acid synthesis by hormones in vivo and in vitro, and the action of hormones on isolated nuclei where the activity of the DNA-dependent RNA polymerase is stimulated.
Abstract: Regulation of gene expression, i.e. the reading of the genetic message, is of great importance for many vital processes. According to Jacob and Monod, genes are regulated by a “repressor” (a protein) which may interact with an “inducer” (a small molecule). In higher organisms, hormones often function as inducers. Evidence stems from (i) the induction of puffs in giant chromosomes by the insect hormone ecdysone, (ii) the stimulation of nucleic acid synthesis by hormones in vivo and in vitro, (iii) the induction of enzymes by hormones, e.g. cortisol, and (iv) the action of hormones on isolated nuclei where the activity of the DNA-dependent RNA polymerase is stimulated. This is most probably due to an increased template activity of the chromatin. — The implication of these findings for developmental processes are discussed.

Journal ArticleDOI
TL;DR: The RNA fraction from the tumor virus appears to affect protein synthesis prior to polysome formation, and was observed when natural messenger RNA, bacteriophage RNA and polycytidylic acid were used to direct peptide synthesis.

Book ChapterDOI
TL;DR: The role of nuclear proteins in gene expression is of great importance, though still very obscure, and their consideration inevitably brings back again to Miescher's original observations on the salmon.
Abstract: Publisher Summary This chapter presents an overview on nucleic acids. The first development of the nucleic acid is tetranucleotide hypothesis, according to which DNA was built out of a great many tetranucleotides each containing one mole of each of the four chief bases; the second is the view that DNA is peculiar to animal cells and RNA to plant cells. The presence of RNA in a few animal tissues had been recorded, but unequivocal evidence has been obtained from ultraviolet spectrophotometry histochemical observations and chemical investigations that RNA is a general constituent of animal, plant, and bacterial cells. The role of nuclear proteins in gene expression is of great importance, though still very obscure, and their consideration inevitably brings back again to Miescher's original observations on the salmon.