Showing papers on "Regulation of gene expression published in 1973"

Organization, transcription, and regulation in the animal genome.

Abstract: This review concern recent experimental information areas of animal cell molecular biology which are relevant to the mechanism of gene regulation. New data regarding interspersion and clustering of repetitive sequence elements in DNA are considered Molecular characteristics of animal structural genes and mRNAs are discussed, with particular reference the frequency of structural gene sequences, mRNA turn over and the interpretation of dipteran complementation groups. The molecular characteristics of nuclear RNAs, the primary transcription products, are reviewed. Evidence for transcription level regulation is summarized and the relation of nuclear and mRNA examined. The protein activator branch of the Britten-Davidson model for gene regulation is further developed and considered in light of current knowledge.

The 5-Methylcytosine in DNA of Rats

Abstract: The GC content and amount of 5-methylcytosine (5-MeCyt) have been determined in total DNA from certain organs of male albino rats 1, 12 and 28 months of age. A marked tissue specificity of DNA with re

Hormonal regulation of gene expression in mammary cells.

Abstract: Publisher Summary This chapter discusses hormonal regulation of gene expression in mammary cells. During pregnancy, the mammary gland undergoes remarkable developmental changes related to the organogenesis of an excretory gland that will form and secrete the specialized components of milk after parturition. This complex process of growth and differentiation is regulated by a large number of intracellular molecular mechanisms, which in turn are governed by a complex set of specific hormonal signals. The chapter reviews the recent studies on the hormonal regulation of gene activation during mammary cell differentiation. These studies have demonstrated a complex sequence of molecular events that lead to the activation of specific genes. They have also delineated the roles of a number of hormones in this process of gene activation. Growth of the mammary gland proceeds through a process of cell proliferation rather than by hypertrophy of existing cellular units. Moreover, it has been found that several hormones regulate the proliferation of mammary epithelial cells in organ cultures.

Developmental and Biochemical Genetics of Lactate Dehydrogenase Isozymes in Fishes

Abstract: The differential regulation of gene function is a fundamental aspect of cellular differentiation. Isozymes (multiple molecular forms of an enzyme, Markert and Moller, 1959) are ideal gene products for the analysis of gene activation during embryogenesis.

Modification of Expression of the Testicular feminization (Tfm) Gene of the Mouse by a “Controlling Element” Gene

Abstract: THE X-linked Testicular feminization (Tfm) mutation of the mouse1 gives a totally noninducible phenotype to all the divergent target organs of testosterone in affected Tfm/Y ♀2–7. When all the previous studies are considered together, the nuclear-cytosol receptor protein which shows a higher binding affinity to 5α-dihydrotestosterone (DHT) than to testosterone (TES) emerges as the most likely candidate for the regulatory protein specified by the Tfm locus. Agreement has not been reached as to the nature of the mutational change affecting the receptor protein, for it has variously been reported to be virtually absent3,8,9, present in normal amounts10, and in excess of normal11 in Tfm/Y target cells.

Evolution of enzyme regulator sites: evidence for partial gene duplication from amino-acid sequence of bovine glutamate dehydrogenase.

Abstract: MODULATION of the biological activity of proteins by metabolite levels is a widespread and well-documented phenomenon. As Monod, Wyman and Changeux1 pointed out, most regulatory protein molecules are composed of several subunits. The regulation of some oligomeric proteins, notably haemoglobin2, involves interaction of similar sites on separate similar subunits. In other cases such as that of aspartate transcarbamylase3 there are separate catalytic and regulatory subunits. Some proteins, however, possess within individual subunits both active sites and regulatory sites capable of mediating homotropic and/or heterotropic interaction.

Flow of information and gene activation during antibody synthesis

Abstract: During this conference different types of immunologically relevant RNAs will be discussed. I will refer only to a certain type of informational RNA that has a molecular weight of approximately 2 X 106. I will also present a scheme concerning the flow of information and the activation of genes during antibody synthesis. This proposal must remain incomplete in the sense that transfer factor, immunogenic RNA, and other types of informational RNA are not incorporated into my scheme. Before discussing the current stage of our knowledge concerning the flow of information and gene activation, I will supply some details on the preparation and on the basic properties and functions of the components of the scheme.

Regulation of gene expression in Salmonella phage P22. I. Genetic experiments involving P22 and Px1.

Abstract: SummaryTransactivation of three early and one late acting gene in the Salmonella phage P22 has been demonstrated through complementation of superinfecting P22 amber mutants. Two different experimental systems were used:(1)Salmonella typhimurium lysogenic for the hybrid phage Px1 which carries genes for early functions and lysozyme synthesis derived from P22. This transactivation occurs in the presence of prophage immunity.(2)Nonimmune Salmonella typhimurium lysogens carrying P22 prophages deleted in their right arm.

Mechanism of Glucocorticoid Hormone Action and of Regulation of Gene Expression in Cultured Mammalian Cells

Abstract: To understand the mechanism of gene expression in higher organisms we have been studying the hormonal regulation of specific protein synthesis in mammalian cells. Most of our work has involved cultured rat hepatoma (HTC) cells (Thompson et al., 1966) in which glucocorticoid hormones influence, as far as we know, only five functions (Table 1). Of these, the induction of tyrosine aminotransferase (TAT) synthesis has been the most extensively studied. A factor which promotes cell adhesiveness (Ballard and Tomkins, 1969, 1970) is also included, as well as under special circumstances, glutamine synthetase (Kulka et al., 1972). Finally, preliminary reports suggest that glucocorticoids increase the amount of phenylalanine t-RNA (Yang, Lippman and Thompson, unpublished) and decrease the activity of the phosphodiesterase which degrades adenosine-3′, 5′cyclic monophosphate (cAMP) (Manganiello and Vaughan, 1972).

Evolution of 9S mRNA Sequences

Abstract: It is already clear that isolated messenger RNA’s (mRNA’s) are potentially very useful tools for the elucidation of gene regulation and chromosomal structure. In this paper we shall look at mRNA from a different standpoint and consider some experiments with histone mRNA which may shed some light on the evolution of protein coding DNA sequences.

Initiation of Protein Synthesis in Prokaryotes

Abstract: Initiation of protein synthesis appears to be a process of great complexity in both prokaryotic and eukaryotic systems. A possible reason for such complexity, particularly in comparison with the process of elongation of nascent proteins, may reside in gene regulation operating through the selection of mRNA or cistrons by ribosomes and protein factors. It is known that in prokaryotes the main control occurs at the transcriptional level. However, for polycistronic mRNA’s there are a few facts consistent with a regulation at the translational level, and this is particularly shown in the case of RNA phage infection of E. coli (MS2, Qs, R17) where the three cistrons of the phage RNA are translated with different frequencies in vivo [1] although they are present in equal concentrations. Therefore, it is conceivable that a control exists at the translational level which might have a specific function in fine regulation of bacterial protein synthesis.

Regulation of Early mRNA Synthesis in Bacteriophage T4-Infected Bacteria: Dependence on Bacteriophage-Specific Protein Synthesis

Abstract: The mechanism of the transcriptional turn-off was studied for those species of mRNA in T4 infection which specify early phage proteins. Total synthesis of these early RNA species was determined by short-time labeling with uracil-5-(3)H after the infection of Escherichia coli B with DNA-negative, conditional lethal mutants, which produce no late mRNA under nonpermissive conditions. With both amber and temperature-sensitive mutants a decrease in incorporation into early RNA by more than 90% was observed within 15 min after infection. Analysis by thin-layer chromatography showed uracil-5-(3)H to enter nucleotide pools throughout the infection cycle. The observed decrease in early RNA synthesis was dependent on protein synthesis, since it could be prevented by chloramphenicol. By varying the time of chloramphenicol addition, the effect of this regulatory protein(s) was found to appear at 3 to 4 min and reached its full extent at 10 to 15 min after infection. The turn-off of transcription of a defined early gene was studied by 5-fluorouracil (FU) rescue of an early, DNA-negative, amber mutant (gene 1, deoxynucleotide kinase) at different times after infection. DNA synthesis could be rescued by FU addition early after infection, but not after 12 min. 5-fluorouracil was efficiently taken up into the nucleotide pools also at late times, as shown by thin-layer chromatography. After incubation in the presence of chloramphenicol from 3 min after infection, DNA synthesis could be rescued as late as 45 min after infection. Thus, when protein synthesis was blocked during the early period of infection, the shut-off of transcription of the studied early gene was prevented.

The Isolation of Genes: A Review of Advances in the Enrichment, Isolation, and in vitro Synthesis of Specific Cistrons

Abstract: Answers to many of the outstanding questions about the biosynthesis of nucleic acids and proteins will require direct studies with isolated genes. These questions include details about: (1) the structure of the gene; (2) the mechanism and regulation of gene expression, and (3) in at least certain cases, post-transcriptional events which modify a primary gene product.

Gene Expression in Fungi

Abstract: This review covers the field of genetic regulatory mechanisms in fungi. Publications on work restricted to the use of actinomycin D and cycloheximide as tools to study regulation of gene expression have been neglected, only investigations using mutants with altered regulatory functions will be discussed. Articles have been chosen to illustrate problems and principles emerging. It has not been attempted to provide a complete bibliography.

The effect of cortisol on biosynthesis and phosphorylation of histones in rat liver

Abstract: Administration of corticosteroid hormones to rats results in an increased activity of several enzymes in liver cells. The induced enzymes are related to the pathway of gluconeogenesis. The mechanism of specific gene activation by hormone action is still not well understood. Recent studies have shown that the steroid hormones combine with specific receptor protein(s) in cytosol of target cells (Jensen et al, 1968; Sherman et al, 1970). The hormone-protein(s) receptor penetrates the liver nucleus and interacts with specific “acceptor sites” of chromatin. These interactions may result in new sites of transcription, i.e. in specific gene activation. It was also demonstrated earlier that the restriction of template activity of chromatin may be due to the presence of the regulatory proteins associated with chromatin (histones) which mask, or repress the function of genome, i.e. play role in gene activation.Although studies on the rate of biosynthesis of histones have given little insight into their phys...

A Transcription Complex from Chloroplasts of Euglena Gracilis

Abstract: Studies on RNA synthesis and the regulation of gene expression in nuclei are hampered by the complexity of the template. Another eukaryotic transcription system is that of the cellular organelles (mitochondria and chloroplasts), whose genomes are small and well defined. We have focused our attention on the transcription of these genomes.

Hormonal Mechanisms in Regulation of Gene Expression

Abstract: Research on the question of how genes are regulated in mammalian cells has accelerated rapidly in the last decade, with much attention being paid to systems in which gene expression is regulated by hormones. Virtually all the hormones have been implicated in this facet of regulation, including those acting via cyclic AMP as intracellular mediator; indeed, there is now firm evidence that cyclic AMP acts to regulate synthesis of specific enzymes in mammalian cells (1,2) as well as in bacteria (3,4). Our recent work, however, has involved hormones which appear to act independently of cyclic AMP, at least in the experimental system we employ. We shall review here some of our recent observations on the mechanisms involved in the stimulation of synthesis of a specific enzyme by the steroid hormone, hydrocortisone, as well as by the polypeptide hormone, insulin. As might be anticipated by the difference in structure of these hormones, we conclude that their mechanisms of enzyme induction are quite different, the steroid acting via a transcriptional mechanism and insulin clearly acting at some post-transcriptional stage of enzyme synthesis. Details of experimental approaches not fully described here can be found in our earlier publications on this work (4–7).

Gene Expression in Liver Endoplasmic Reticulum

Abstract: The study of gene expression in higher organisms is rendered difficult by the complexity of their cells and tissues. In contrast to prokaryotes, where the translation and transcription of genetic information take place in one compartment, in eukaryotes the two processes are separated topologically by the nuclear membrane. In addition, genetic information in these cells is also present, and is utilized, within certain cytoplasmic organelles, notably chloroplasts and mitochondria, and the operation of the nuclear and extranuclear genomes is coordinated by some yet unknown mechanisms; this topic was the subject of an excellent symposium held here in Australia in late 1969 (cf. Boardman et al., 1971). The association of many enzyme functions with various intracellular membranes also calls for a coordination of protein synthesis within the synthesis of other membrane constituents, primarily phospholipids (Ernster and Orrenius, 1965; Siekevitz et al., 1967; Siekevitz, 1972). A further complexity in multicellular organisms exists in the form of a regulation of gene expression between different cells and tissues by means of environmental, neural and hormonal stimuli (Knox et al., 1956; Tata et al., 1963; Tata, 1967a,b; Greengard, 1970; Knox, 1972).

Cell Models and the Homeostasis Problem

Abstract: In mammalian cells initiation of DNA replication requires RNA synthesis in the early G1 — phase and synthesis of an inducer during the S — phase. The mitotic operon may be switched on and off by an operonic trigger which in turn is based upon the mitotic operon and the histospecific operon. The assumption of a block of the two operon activities during the S — phase guarantees the oscillatory action of the trigger. The model contains the feedback with the total cell number via the repressor for the histospecific operon. Taking into account a competition for micromolecular precursors between the processes implied in protein synthesis and enzymatic reactions, a single micromolecular precursor for protein synthesis suffices which is synthesized under the control of an enzyme (as far as steady state can be assumed) and for whose decay a lytic enzyme is required in addition. The amount of gene activation is determined by the switching states of certain triggers. For all-or-none triggers one may adopt binary (logical) functions (2). The gene activities which enable the different kinds of work done by stem cells (low proliferation), immature cells (high proliferation), mature cells (high histospecificity) and dying cells, can be obtained by a system of triggers. In the model of cell cycle the cell volume must be included, too. The initiation of DNA replication can be considered as due to accumulation of a threshold membrane substance. The feedback between growth rate and the numbers of i-type cells (i.e. stem-immature-, mature or dying cells) can be considered as following (3) with intercellular diffusion of the chalone. A pair of equations is obtained which describes: 1. the intra-extra-cellular exchange of chalones for cells of this type and 2. the balance of the extracellular chalone being subject to a decay of certain rate. The model neglects many aspects of cell regulation. However, since DNA transription is the first amplifying cascade in the sequence of DNA → RNA → enzyme → enzymatic reaction the consideration of gene activation control can be regarded only as a first approximation which must be elaborated further.

Studies on the Template Specificities of Eukaryotic DNA-Dependent RNA Polymerases in Vitro

Abstract: Investigations of bacteriophage infection of Eschenichia coli have established a role for the DNA-dependent RNA polymerase in the regulation of gene expression. It is now generally accepted that host E. coli RNA polymerase transcribes at least a part of the phage genome (the ‘early’ regions) whereas a modified host RNA polymerase (in the case of T4) or even a new phage-specified polymerase (as in the case of T7) transcribes the ‘late’ regions (Travers, 1971; Bautz, 1972). These observations suggest that the host E. coli RNA polymerase, the modified T4 polymerase and the new phage-specified polymerase recognize different nucleotide sequences and thus bind to and transcribe from different initial binding sites (promoter sites) on the phage DNA. Thus at least one “positive” control mechanism resides in the ability of different polymerase species to recognize different promoter sites.