Showing papers on "Regulation of gene expression published in 1972"

Gene Therapy for Human Genetic Disease

Abstract: In our view, gene therapy may ameliorate some human genetic diseases in the future. For this reason, we believe that research directed at the development of techniques for gene therapy should continue. For the foreseeable future, however, we oppose any further attempts at gene therapy in human patients because (i) our understanding of such basic processes as gene regulation and genetic recombination in human cells is inadequate; (ii) our understanding of the details of the relation between the molecular defect and the disease state is rudimentary for essentially all genetic diseases; and (iii) we have no information on the short-range and long-term side effects of gene therapy. We therefore propose that a sustained effort be made to formulate a complete set of ethicoscientific criteria to guide the development and clinical application of gene therapy techniques. Such an endeavor could go a long way toward ensuring that gene therapy is used in humans only in those instances where it will prove beneficial, and toward preventing its misuse through premature application. Two recent papers have provided new demonstrations of directed genetic modification of mammalian cells. Munyon et al. (44) restored the ability to synthesize the enzyme thymidine kinase to thymidine kinase-deficient mouse cells by infection with ultraviolet-irradiated herpes simplex virus. In their experiments the DNA from herpes simplex virus, which contains a gene coding for thymidine kinase, may have formed a hereditable association with the mouse cells. Merril et al. (45) reported that treatment of fibroblasts from patients with galactosemia with exogenous DNA caused increased activity of a missing enzyme, alpha-D-galactose-l-phosphate uridyltransferase. They also provided some evidence that the change persisted after subculturing the treated cells. If this latter report can be confirmed, the feasibility of directed genetic modification of human cells would be clearly demonstrated, considerably enhancing the technical prospects for gene therapy.

General Theory of Chromosome Structure and Gene Activation in Eukaryotes

Abstract: This simple theory provides a function for non-histone proteins and an explanation for the large size of eukaryotic genomes, repetitive sequences in DNA, HnRNA and “processing” of nuclear RNA.

Chromosomes Isolated from Unfixed Salivary Glands of Chironomus

Abstract: The strategy of cell differentiation is based primarily on the principle of differential gene activation. With any mechanism of differential gene activation, the final processes leading to the activity of a gene occur at the level of the chromosome. Discussion about the probable nature of these final processes, and the intermediates involved therein, will end with experiments in which such processes prove to be operational in isolated chromosomes. Using regular chromosomal material, the gene specificity of an activation process is difficult to establish. However, with polytene chromosomes of salivary glands from Chironomus this can be done easily and precisely. These chromosomes exhibit a very characteristic banding pattern and are so big that they can be isolated even by freehand micro-manipulation. Thus, they represent an ideal tool for studying differential gene activation at the chromosome level.

Chapter 1 The Structure of Transcriptional Units In Eukaryotic Cells

Abstract: Publisher Summary This chapter discusses the difference between eukaryotes and prokaryotes in many respects. First, they have then nuclei separated by a membrane from the cytoplasm. This membrane effectively separates transcription, which takes place in the nucleus, from translation, which proceeds mainly in the cytoplasm. Thus, transcription and translation in eukaryotes are uncoupled and for this reason an additional step in gene expression appears— namely, mRNA transport. Second, in eukaryotes the process of the regulation of gene expression is complicated. Various cells differ greatly in their properties, and these differences are stable and do not depend on the conditions of the medium— that is, the cells are differentiated. Third, the chromosomes in eukaryotes contain many proteins. In particular, the strongly basic proteins, histones, are complexed with the DNA. This may be connected with the appearance of differentiation and the general complication of the regulatory processes. This chapter describes the patterns of transcription in eukaryotic cells. Different models of the transcriptional unit in eukaryotic cell are discussed in the chapter to describe the nature of dRNA2 or dRNA that is degraded inside the cell nucleus. General aspects of the regulation of transcription in eukaryotes and the role of chromosomal protein are also discussed in this chapter.

Gene activation during early development of mammals.

Abstract: The preimplantative stage of development has as yet not been studied extensively; most data were derived from the mouse and the rabbit. In this article, the results on macromolecular synthesis during this period of development are summarized. In the beginning, the embryonic genome is apparently genetically inactive; early development is governed by maternal storage products transmitted through the egg cytoplasm. Activation of embryonic genes occurs step-wise, with the protein synthesizing apparatus being produced first. Synthesis of individual proteins (enzymes) coded for by embryonic genes apparently in general does not start before the middle blastocyst stage, shortly before implantation. It is discussed whether cytoplasmic storage products take part in gene activation during this period.

Preferential inhibition by proflavine of the hormonal induction of glutamine synthetase in embryonic neural retina.

Abstract: The hormonal induction of glutamine synthetase (EC 6.3.1.2) in embryonic neural retina tissue in vitro is blocked preferentially and reversibly by proflavine (3,6-diaminoacridine) in the absence of cell or DNA replication; cell viability is not affected, and the synthesis of total cellular proteins and RNA is only slightly reduced. In the induction of this enzyme, there is a rapid increase in the synthesis and accumulation of the enzyme selectively elicited by the steroid inducer; for this effect, transcription is essential. Radioimmunochemical measurements have shown that proflavine inhibits induction by prevention of de novo synthesis of catalytically active and immunologically reactive glutamine synthetase protein. It does not measurably affect the uptake of the steroid inducer by the retina cells. Since the translation of this enzyme by preformed RNA templates is not stopped by proflavine, the inhibitory effect of proflavine on induction is apparently due to interference with transcriptional or pretranslational processes required for the provision of active transcripts for enzyme synthesis. The finding that proflavine inhibits preferentially a tissue-specific, inducible differentiation in postmitotic embryonic neural cells offers new approaches to the study of regulation of gene expression in eukaryotes.

Aldosterone-induced alterations in the synthesis of renal cortical chromatin components and acetylation of histones.

Abstract: SummaryThis investigation was undertaken in order to obtain some knowledge of the mechanism by which aldosterone brings about known increases in the rates of RNA synthesis in the nuclei of the kidney cortex by attempting to study the changes in the synthesis of the chromatin components as well as changes in the acetylation of histones. Specificity of gene activation and repression in eukaryotes is believed to involve these chromatin components and the acetylation of histones. The present data suggests that following aldosterone administration there appears to be a generalized sequential increase in the synthesis of the nonhistone proteins, RNA, and histones in the chromatin material. Furthermore the mineralocorticoid treatment leads to a very early increase in the rate of histone acetylation.

Topology of DNA and N gene expression in coliphage lambda.

Abstract: In a transformation system designed to assay gene function from the infecting DNA we find that the intact λ molecule is necessary to provide N function, whereas the phage recombination (red) genes can function from half as well as whole λ molecules. Our results may reflect the need of a circular template for efficient N gene transcription in vivo.