Showing papers on "Regulation of gene expression published in 1978"

Cell division from a genetic perspective

Abstract: A novel view of the eukaryotic cell cycle is taking form as genetic strategies borrowed from investigations of microbial gene regulation and bacteriophage morphogenesis are being applied to the process of cell division. It is a genetic construct in which mutational lesions identify the primary events, thermolabile gene products reveal temporal order, mutant phenotypes yield pathways of causality, and regulatory events are localized within sequences of gene controlled steps.

Irreversible gene repression model for control of development

Abstract: As the pluripotent cells of early embryos differentiate, each progressively loses the potency to develop into several phenotypes. Ultimately, each cell becomes irreversibly restricted to the expression of a single phenotype. Although in many instances details regarding those restriction events are well known, there is little information concerning the nature of the gene transcription changes involved. A model that accounts for the diminution of developmental potential as resulting from progressive, irreversible repression of previously active genes is presented. A scheme of progressive gene repression, rather than selective gene activation, is most consistent with observations from experimental embryology as well as from more recent biochemical experimentation.

Multilocus enzymes, gene regulation, and genetic sufficiency

Abstract: Moderately diverged small sets of nonallelic genes that control one type of protein, such as genes for isozymes, are usually considered to be present in order to permit adaptations of protein function to local conditions in organismal time and space. However some irregularities, as well as some regularities, in the distribution of lactate dehydrogenase isozymes seem difficult to reconcile with this view. A complementary interpretation is based on selection for gene regulation. Irrespective of the relative importance of transcriptional control and of control through processing of the transcripts, regulatory patterns in higher organisms may be explored on the basis of formal relationships between molecular components interacting within and between “controller nodes”. It is shown that an analysis in terms of controller node stability states may account for the variations in regulation of isozyme synthesis. Adaptive changes in regulatory sequences may insure the stability of the synthesis of a given type of protein in the face of developmental, as well as evolutionary, alterations in patterns of gene activity, correlated with the evolution of cell differentiation. It is proposed that gene duplication, beyond the addition of novel functions to the established ones, plays a further and rather opposite role. This role is to maintain theconstancy of established protein functions in the presence of developmental and evolutionary change. To this effect the duplication of functional units of gene action, rather than merely of coding sequences, is likely to be required.

Organization of Immunoglobulin Genes

Abstract: The nucleotide-sequence determination of a cloned, embryonic Vlambda gene directly demonstrated that V genes are separate from a corresponding C gene in embryonic cells. Analysis by restriction enzymes of total cellular DNA from various sources strongly suggested that the two separate immunoglobulin genes become continuous during differentiation of B lymphocytes. There seems to be a strict correlation between the joining event and activation of the joined genes. Cloning of more immunoglobulin genes from embryo and plasma cells will not only provide direct demonstration of such a gene-joining event but also help in the elucidation of a possible relationship of the event to gene activation mechanisms.

Assessment of specificity of oestrogen receptor-DNA interaction by a competitive assay.

Abstract: ALTHOUGH hormonal regulation of gene expression and the nature of specific interactions between steroid hormone receptor and genome have attracted growing interest1–5, very little is known about the molecular nature of receptor–DNA interaction4–6. As a first step in unravelling the specificity and the dynamics of the interaction between uterine oestrogen receptor and DNA7–11, we have selected a well defined model system: a synthetic DNA and DNA–cellulose competition assay. We have found that the AT-rich segment of the double stranded DNA in its intact conformation is required for optimum receptor binding. We have examined oestrogen receptor binding to synthetic DNA with well defined sequences, and determined whether the receptor favours double-stranded or single-stranded regions of the DNA (unwinding protein generally binds preferentially to single-stranded DNA12). Finally, we have studied the effect of an intercalating drug, actinomycin D, on the receptor binding.

Gene regulation in adaptive evolution.

Abstract: It has been suggested that gene regulation may play a critical role in adaptive evolution. However, gene regulation has proved to be most refractory to experimental investigation in multicellular organisms. Using specially constructed stocks of Drosophila melanogaster, we have demonstrated the following. (1) The existence in natural populations of ample variation in regulatory genes that modify the activity of alcohol dehydrogenase (ADH), an enzyme coded by a structural gene locus, Adh, located on the second chromosome; the regulatory genes are located on the third chromosome, and thus are not adjacent to the structural locus. (2) The regulatory genes act not by means of post-transcriptional or post-translational modification of the gene product, but rather by controlling the number of ADH molecules; this is consistent with the hypothesis of gene regulation by means of macromolecules specifically binding at control sites adjacent to the structural gene locus. (3) The variation in regulatory genes is adaptively significant; adaptation to higher levels of environmental alcohol takes place not by changes in the Adh structural locus, but by changes in regulatory genes that control the number of ADH molecules in the organisms. Our results provide direct evidence of the importance of gene regulation in eucaryotic evolution.

Genetic Analysis of the Gene for N-Acetylglucosaminidase in DICTYOSTELIUM DISCOIDEUM

Abstract: Three independent mutations affecting N-acetylglucosaminidase in Dictyostelium discoideum were mapped by the parasexual system and found to lie on linkage group IV. These mutations as well as two others were found to be recessive and noncomplementing in heterozygous diploids. Thus they all appear to affect the nagA locus. Since two of the mutations give rise to thermolabile enzyme, this defines the structural gene for N-acetylglucosaminidase. The enzyme is a homodimer of a 68,000 dalton subunit and thus would be expected to be determined by a single locus. The expression of this gene is regulated by the stages of development; however, it should be mentioned that none of the mutations fell in a separate locus that might determine a specific positive regulatory protein.

On the Regulation of Gene Expression: Incompatibility in Schizophyllum

Abstract: A new functional class of nucleic acids is postulated on the basis of the multiallelic incompatibility system regulating sexual morphogenesis in the higher fungi. A physical-chemical basis for distinguishing molecules active, as opposed to inactive, in promoting morphogenesis is established by the secondary structure of the resultant nucleic acid duplexes. This regulatory mechanism may be of broad import.

Approaches to Problems of Gene Regulation and Cell Type Determination in Amphibians

Abstract: SYNOPSIS. In order to understand development it is necessary to elucidate the mechanisms behind both gene regulation and cell type determination. I have approached these problems in three ways utilizing the amphibian system. The first involves the injection of somatic cell nuclei into oocytes. The oocytes are used as a coupled transcripuonal-translational system to detect the translational products of the injected nuclei. In this way it becomes possible to examine the regulation of genes coding for ubiquitous or housekeeping functions as well as those coding for differentiated functions. The results indicate that in the case of the proteins examined, the oocyte cytoplasm appears to be able to regulate the synthetic activity of the transferred nuclei so as to conform to its own synthetic output. A second approach involves the examination of the expression of various classes of genes in interspecific amphibian hybrids. These studies show that there appears to be preferential expression of the maternal allele of a differentiated product, alcohol dehydrogenase, while the maternal and paternal alleles of ubiquitous products such as lactate dehydrogenase and superoxide dismutase are expressed simultaneously. These results suggest that there may be differences in the regulation of various classes of genes. The third approach involves the injection of bacterial plasmids containing eukaryotic genes into amphibian oocytes. A plasmid, pSp2, containing sea urchin histone genes HI, H2b, and H4 was injected into the germinal vesicle of Xenopus laevis oocytes. The genes coding for sea urchin histones HI and H2b were expressed. The applicability of this system to problems of gene regulation and cell type determination is discussed.

Regulation of Gene Expression in the Nucleus by Gonadotropins

Abstract: For the past 15 years or so, I have been providing evidence that polypeptide hormones stimulate hormone-specific species of glucose-6-phosphate dehydrogenase (Glc-6-PD) in their target tissues. This allosteric regulation of the rate-limiting enzyme of the pentose phosphate cycle provides reducing equivalents for biosynthetic purposes. In addition, it provides ribose sugars such as 5-phospho-d-ribosyl pyrophosphate (5-PRPP) that are rate-limiting to the synthesis de novo of purine and pyrimidine nucleotides. These nucleotides are required in the synthesis of RNA and DNA and in electron- and energy-carrying compounds, such as NADPH and ATP.

DNA-binding proteins of psoriatic scales III. Biochemical characterisation as non-histone-proteins.

Abstract: Histone and non-histone-proteins (NHP) are proteins with a specific affinity to DNA; each group is involved in the regulation of gene expression in its own way. To investigate molecular biologic processes at psoriasis, DNA-binding proteins (DBP) were isolated from psoriatic scales. During this work the proportions of histone and NHP of the DBP fractions were examined. Using two different methods (Bio Rex 70-chromatography and isoelectrofocussing), it was found that the isolated DBP contain only acidic proteins. Likewise, the composition of amino acids is comparable with those of acidic, nuclear proteins of other tissues. Thus the isolated DBP represent to its greatest extent acidic, chromosomal NHP, which obviously are derived from the preserved nuclei of the parakeratotic scale layer.

Mechanism of Action of Gonadotropins and the Regulation of Gene Expression

Abstract: Growth and maturation of the ovary, culminating in the onset of complete and cyclic ovulation as well as functional steroidogenesis, are clearly some of the most profound physiological changes that occur during the postnatal development of the female. The postnatal developmental period is characterized by the acquisition of new functions that necessitate the induction of specific cellular proteins partaking in the diversity of ovarian function. The induction of new specific ovarian proteins during the period of postnatal differentiation requires mechanisms that conceivably involve selective activation and derepression of genetic information residing in the genome. It implies both a selection and restriction of DNA function, with specific regions of the repressed genome being called into activity in the various ovarian cells, resulting in synthesis of specific species of RNA and of specific cellular proteins that reflect the degree of differentiation of the ovary.

Regulation of gene expression in normal and neoplastic cells

Abstract: We have been studying the regulation of two sets of genetic sequences-histone genes in human cells and AKR C-type viral sequences in mouse cell lines. Histone genes: Recently we observed the presence of two species of H4 histone mRNA on the polysomes of S phase HeLa S 3 cells. Electrophoresis under denaturing and non-denaturing conditions indicate that the two H4 mRNAs differ in size. Both mRNAs translate H4 histones in vitro , lack poly A at their 3′ termini and are capped at their 5′ termini. Polyacrylamide gel electrophoresis and tryptic peptide analysis suggest that the polypeptides synthesized by the two mRNAs are similar. T1 digests of the two H4 mRNAs and two-dimensional fractionation of the resulting oligonucleotides suggest some differences in the nucleotide sequences. The possible biological significance of the two H4 histone mRNAs is discussed. RNA tumor viruses: The expression of AKR C-type RNA tumor virus has been studied in cell lines derived from AKR mouse embryos. Although all AKR cell lines examined contain the proviral sequences integrated into their genomes, viral producer and non-producer lines have been identified. Using a 3H-labeled DNA complementary to AKR viral RNA sequences, the presence of viral RNA sequences in the nucleus and cytoplasm of viral producer cells has been detected. Chromatin from viral producer cells is an effective template for transcription of AKR viral RNA sequences. A significantly reduced level of hybridization is observed between AKR viral cDNA and nuclear RNA, cytoplasmic RNA and in vitro chromatin transcripts from non-producer AKR cells. Regulation of viral gene expression mediated at least in part at the transcriptional level is therefore suggested. The low level of hybridization of viral cDNA with in vivo and in vitro transcribed RNAs from non-producer cells may reflect either partial AKR viral transcripts or other endogenous, closely related C-type viruses. Although chromatins of viral producer and non-producer cells differ in their ability to transcribe AKR viral sequences, high resolution two-dimensional analysis of chromosomal proteins from both cell types does not reveal significant differences.

Gene regulation of the lactate dehydrogenase isoenzyme spectrum in the mouse liver

Abstract: The isozyme pattern of lactate dehydrogenase (LDH) was studied by means of electrophoretic and immunochemical methods in liver of inbred mouse strains: CBA/Lac, DBA/1J, DBA/2J, AKR/J, C57BL/6J, C3H/He Interstrain polymorphism for the activity of LDH isozymes in mouse liver is found to take place, which is due to the presence of the regulatory gene Ldr-2 Based on the breeding data of DBA/2J and CBA/Lac mice, which show different liver LDH patterns, and judging by the results of the immunochemical analysis, it is suggested that the low activity of LDH isozymes containing subunit B and controlled by the gene Ldr-2 is inherited codominantly It is found that the effect of the gene Ldr-2 is independent on that of the gene Ldr-1, which modifies the phenotypic expression of the gene B of erythrocyte LDH in mice The gene Ldr-2 is in the same linkage group as the gene Ldr-1, at a distance of 196 map units from it The data of immunochemical analysis suggest that the effect of the gene Ldr-2a is related with the decreased content of the subunit B, and possibly of the subunit A of LDH The study of LDH pattern throughout mouse development has demonstrated, that the differences in liver KDH patterns between CBA/Lac and DBA/2J mice, controlled by the gene Ldr-2, express phenotypically on 6-8 dyas and are finally formed in the middle of the first month of the life