Showing papers on "Regulation of gene expression published in 1971"
TL;DR: These findings indicate that the Gpi-1 paternal locus is expressed by day 5, and demonstrate the value of using electrophoretic variants to pinpoint synthesis of new enzyme which may not be reflected in changes in levels of activity.
122 citations
TL;DR: The examination of the pattern of gene expression and its regulation revealed that the behavior of the key gluconeogenic and glycolytic enzymes exhibits an antagonistic pattern during differentiation, under hormonal regulatory conditions and in neoplasia.
90 citations
TL;DR: It is assumed that there exists an initial divergence in genetic activity due to an unequal distribution of egg cytoplasmic regulatory elements among the different cells in early cleavage and that individual cells would differ in their response to external inductive agents arising, for example, in nearby cell layers.
79 citations
Book Chapter•
01 Jan 1971
TL;DR: This report was submitted the same year that the Genetics Research Unit closed and McClintock was awarded National Medal of Science.
Abstract: This report was submitted the same year that the Genetics Research Unit closed and McClintock was awarded National Medal of
Science
46 citations
TL;DR: It is reported that RNA-dependent DNA polymerase also behaves in this way when the addition of phytohaemagglutinin or other mitogens transforms lymphocytes into actively proliferating cells.
Abstract: RNA-DEPENDENT. DNA polymerase an activity initially thought to be unique to RNA tumour viruses1–3, is now known to be present in normal human lymphocytes4, which are differentiated and seldom divide in vivo or in culture. The addition of phytohaemagglutinin (PHA) or other mitogens (including appropriate antigens) transforms lymphocytes into actively proliferating cells5. Several enzymes which function in gene activation and DNA replication specifically increase in activity during this transformation6,7. We now report that RNA-dependent DNA polymerase also behaves in this way.
41 citations
TL;DR: This review describes the results of hybridizing cells in such combinations as between cells of different species, between differentiated and undifferentiated cells, and between mutant and normal cells.
Abstract: Hybridization of somatic mammahan cells in vitro was first observed in 1960 (1), at a time when experiments on the control of enzyme synthesis in bacteria were demonstrating the importance of recombinational systems for the analysis of genetic regulatory mechanisms (2). The discovery of ~ recombinational system for mammalian cells therefore suggested a new approach to the investigation of the mechanisms of the regulation of gene expression in these cells. This approach involves the combination in a hybrid of the genomes of two cells which differ in various functions and the analysis of the mechanisms underlying the differences in terms of interactions between the genomes in the hybrids. Analyses of this type have been performed on hybrids between cells of different species, between differentiated and undifferentiated cells, and between mutant and normal cells. The results of hybridizing cells in such combinations are described in this review.
41 citations
TL;DR: Experiments suggest that gene activation is dependent upon specific acidic nuclear proteins, whose synthesis is regulated at the post-transcriptional level.
Abstract: Confluent monolayers of human diploid fibroblasts can be stimulated to synthesize DNA and divide by a change of medium In the lag period between the application of the stimulus and the onset of DNA synthesis, there occurs a series of biochemical events which include the very early activation of the cell genome Gene activation requires protein synthesis but not previous RNA synthesis Experiments suggest that gene activation is dependent upon specific acidic nuclear proteins, whose synthesis is regulated at the post-transcriptional level
41 citations
TL;DR: The reliable detection of “new” antigens in man would provide an immunological signal of incipient tumour formation and might permit early or more precise diagnosis, as well as suggest improved means of treatment.
Abstract: THE occurrence of tumours or leukaemia in experimental animals is frequently associated with the appearance of “new” antigens perhaps indicative of gene activation or mutation, or infection with oncogenic virus. The reliable detection of such antigens in man would provide an immunological signal of incipient tumour formation and might permit early or more precise diagnosis. The study of human tumour antigens might also be expected to yield information about the causes and natural history of human cancer as well as suggest improved means of treatment. This communication is concerned with the detection of one group of “new” antigens, those associated with human leukaemia.
37 citations
TL;DR: It is shown by RNA-DNA hybridization that each tissue contains a distinct population of chromosomalRNA sequences, compatible with the proposal that chromosomal RNA is involved in the process of gene activation.
Abstract: Chromosomal RNA was isolated from several rat tissues by a new technique. It is shown by RNA-DNA hybridization that each tissue contains a distinct population of chromosomal RNA sequences. This finding is compatible with the proposal that chromosomal RNA is involved in the process of gene activation.
27 citations
TL;DR: The finding that more histones are associated with the chromosomal DNA of higher organisms than with that of lower organisms is consistent with the suggestion that histones act as suppressors in the regulation of gene expression in cellular differentiation as mentioned in this paper.
Abstract: THE finding that more histones are associated with the chromosomal DNA of higher organisms than with that of lower organisms1–4 is consistent with the suggestion5 that histones act as suppressors in the regulation of gene expression in cellular differentiation. Thus histones must have been acquired at some stage in the evolution of differentiated eukaryotic organisms from the primitive prokaryon.
21 citations
TL;DR: The general principles used by Jacob and Monod in their study of negative regulation were extended to positive regulation by Englesberg et al. (1965) and an independent approach permitted the discovery of positive controls in temperate bacteriophages.
Abstract: The expression of many bacterial genes adapts itself in an almost instantaneous and reversible way to specific environmental changes. More specifically, the concentration of a number of metabolites, a function of the amounts of enzymes involved in their synthesis or degradation, in turn retroacts on the rate of synthesis of these enzymes. The genetic bases for this regulation were established by Jacob and Monod (1961). These authors also showed how the known elements of these regulatory mechanisms could be connected into a wide variety of circuits endowed with any desired degree of stability, in order to account for essentially irreversible processes like differentiation (Monod and Jacob, 1961). The general principles used by Jacob and Monod in their study of negative regulation were extended to positive regulation by Englesberg et al. (1965). An independent approach permitted the discovery of positive controls in temperate bacteriophages (see below, III).
TL;DR: Although the authors' models are neither adult organisms nor developing embryos, the regulatory mechanisms which operate in them can help in understanding more complex developmental processes and alterations in cellular physiology of intact higher organisms.
Abstract: In the developing embryo, a complex program of gene activation and inactivation unfolds which produces the final differentiated end-state of the organism. Furthermore, since the genetic potential is identical in each cell of an adult metazoan, differences in cell phenotype must result from differential expression of these genes. It is the purpose of the present article to discuss some possible molecular mechanisms which might underly the processes of development, differentiation, and enzyme induction. Some of the conclusions are based on work in model systems, in which certain aspects of gene regulation can be more easily studied. Although our models are neither adult organisms nor developing embryos, the regulatory mechanisms which operate in them can help in understanding more complex developmental processes and alterations in cellular physiology of intact higher organisms.
01 Jan 1971
TL;DR: These observations indicate that neither X chromosome of the female mammalian cell is condensed during the very early stages of development, which may help explain why some humans with sex-chromosome anomalies have phenotypic abnormalities even though their mature somatic cells have only one genetically active X chromosome, like the cells of chromosomally normal individuals.
Abstract: Summary This is a review of experiments which attempt to explore mechanisms of gene regulation during preimplantation development in mammals. The time of appearance and rate of formation of sex chromatin are compared with the patterns of RNA and protein synthesis in somatic cells of female rabbit embryos recovered prior to implantation. In vivo, sex-chromatin formation starts in the rabbit about 84 hours after fertilization (70 - to 800-cell stage). The frequency of sex-chromatin-positive nuclei reaches values of 85 % to 90 % at about 135 hours after fertilization, which is shortly before implantation. Sex-chromatin formation also occurs if washed embryos are allowed to develop in vitro, suggesting that the mechanism initiating sex-chromatin formation is primarily under embryonic and not maternal control. The frequency of sex-chromatin in cultured pieces of dissected embryos depends on the embryonic age (total of hours in vivo between fertilization and recovery plus hours in culture) rather than the number of cells in the embryonic segment, which may vary considerably for different pieces of the same embryo. Other experiments also indicated that the age from fertilization is more consistently associated with sex-chromatin formation than any other variable. Rates of 3H-uridine and 3H-leucine incorporation were determined by autoradiography of single embryos to establish the patterns of RNA and protein synthesis, respectively. RNA synthesis is very active at 60 to 100 hours after fertilization, which precedes the period when most sex-chromatin formation occurs. The pattern of protein synthesis lags behind the pattern of RNA synthesis by about 20 hours, with substantial amounts of protein also being synthesized before most sex-chromatin formation has occured. These observations indicate that neither X chromosome of the female mammalian cell is condensed (and both are presumably active genetically) during the very early stages of development. Since transcription and translation are apparently active at these stages, the genetic information present on both X chromosomes could contribute to the regulation of determination, if this occurs early. Alternately, the information could be transcribed and stored in the form of stable RNA, which would regulate determination and differentiation at a later developmental stage. All this is in accord with expectations based on the Lyon hypothesis and may help explain why some humans with sex-chromosome anomalies have phenotypic abnormalities even though their mature somatic cells have only one genetically active X chromosome, like the cells of chromosomally normal individuals.
TL;DR: The cell fusion technique is used to develop an experimental model for the potential-correction of a specific genetic defect in a living animal.
Abstract: THE fusion of cells by inactivated Sendai virus provides a method for the study of gene regulation in mammalian cells. Two cells, each with a specific enzyme deficiency, have been joined to yield a hybrid cell containing both previously deficient enzymes1, 2. Harris and his co-workers have shown that terminally differentiated chick erythrocyte nuclei, when introduced into HeLa cytoplasm by cell fusion, are “reactivated” and direct the elaboration, by the hybrid cell, of chick proteins3, 4. These in vitro examples of gene complementation in hybrid cells give no indication of the functional significance of the elaborated gene products. We have used the cell fusion technique to develop an experimental model for the potential-correction of a specific genetic defect in a living animal.
TL;DR: It is suggested that large scale acetylation of histones is not required for gene activation during metamorphosis.
Abstract: 1. 1. Histones from all developmental stages of Rana catesbeiana in the liver and erythrocytes were found to be qualitatively similar. 2. 2. Gas chromatographic analysis revealed a decrease in hydrolyzable acetate on the histones as metamorphosis progressed to the adult or on thyroxine treatment. 3. 3. Isotope incorporation revealed a decrease in liver histone acetylation and no change in erythrocyte histone acetylation during metamorphosis. 4. 4. It is suggested that large scale acetylation of histones is not required for gene activation during metamorphosis.
TL;DR: A theory to account for the regulation of gene expression in eukaryotic cells proposes that at least two genes are necessary to regulate the synthesis of a specific protein.
Abstract: We have recently presented a theory to account for the regulation of gene expression in eukaryotic cells (1). This scheme, which explains hormonal enzyme induction and the control of the synthesis of specific mareomolecules by drugs and other environmental stimuli etc., also takes into consideration the variations in enzyme scheme proposes that at least two genes are necessary to regulate the synthesis of a specific protein. The first is a structural gene (G s) specifying the amino acid sequence of the protein in question. The second, a regulatory gene (GR), codes for tile synthesis of a labile post-transcriptional repressor \"R.\" In tile tyrosine amino-
01 Jan 1971
TL;DR: The posttranscriptional regulation of gene expression is a general mechanism found in many developing and inducible systems of eukaryotes and any system in which a paradoxical stimulation of specific protein synthesis is caused by inhibitors of RNA synthesis is quite likely to be subject to a posttrans transcriptional regulation.
Abstract: Publisher Summary
This chapter focuses on the regulation of gene expression in mammalian cells. In mammalian tissues, in fact in most eukaryotic tissues, a recognized predominant action of cyclic AMP (cAMP) is the stimulation of enzymic phosphokinase activities that are responsible for the phosphorylation of proteins. It has been proposed that hormones that activate adenyl cyclase regulate gene activity via the cAMP promotion of histone phosphorylation, the latter permitting more efficient gene transcription than does its non-phosphorylated form. Many attempts have been made to demonstrate that hormones exert their effects on gene expression at the level of gene transcription, analogous to the action of inducers on the lactose operon in Escherichia coli. An integral part of the regulatory mechanisms in prokaryotes is the rapid turnover of messenger RNA molecules. Thus, when specific gene transcription is repressed, the concentration of specific RNA template rapidly falls and the synthesis of the specific protein ceases. Furthermore, the rate of specific protein synthesis is frequently determined only by the concentration of specific template RNA. Any system in which a paradoxical stimulation of specific protein synthesis is caused by inhibitors of RNA synthesis is quite likely to be subject to a posttranscriptional regulation of gene expression. Therefore, it may be that the posttranscriptional regulation of gene expression is a general mechanism found in many developing and inducible systems of eukaryotes.