Glucocorticoid regulation of mouse mammary tumor virus gene expression.

Glucocorticoid hormones act rapidly and specifically to stimulate the synthesis of mouse mammary tumor virus RNA in a variety of mouse mammary tumor cells and infected heterologous cells. The increase in viral RNA production appears to be mediated by receptor proteins and requires the presence of basal levels of viral RNA. Infection of heterologous cells with MMTV may alter host cell responses to glucocorticoids; in addition, production of unintegrated viral DNA in these cells has provided reagents required for studying the structure and function of the viral DNA itself. The advent of new techniques for genetic manipulation of eukaryotic cells and for isolation of large amounts of specific DNA sequences should now permit detailed analyses of steroid hormone action in this system.     

Boundary functions in the control of gene expression.

Recent experiments using stably transformed genes in mouse and Drosophila have demonstrated that elimination of euchromatic position effects can be used as a functional assay for domain boundaries. These studies will lead to an analysis of boundary structure, and in addition will provide clues to the mechanism(s) of gene regulation by higher order chromatin packaging.     

Electrical-ionic control of gene expression

• 1.1. Changes in turgor, in cell volume, in membrane potential, in intracellular ionic activities and, more recently, in spontaneous electrical activity have been reported to be causally linked to the expression of specific genes.
• 2.2. As a result, it has become clear that changes in membrane properties and/or in the intracellular “ionic environment” can play an important role in generating cell type specific physiological responses which indirectly—or maybe directly—affect gene expression.
• 3.3. Possible targets of the ionic “environment” are: the selective transport across biological membranes; the activity of certain (regulatory) enzymes; the conformation of some (regulatory) proteins; of chromatin; of the cytoskeleton; of the nuclear matrix; the association of the cytoskeleton with plasmamembrane proteins or RNA; the association chromatin-nuclear matrix; protein-DNA and protein-protein interactions etc. All these sites may be instrumental to “fine or coarse” tuning of gene expression.
• 4.4. The exact mechanisms by which changes in intracellular ionic environment are transduced, directly or indirectly, into alterations of the activity of trans-acting factors have not yet been fully uncovered. Changes in the degree of phosphorylation of regulatory proteins and/or of trans -acting factors may provoke fine tuning effects on cell type specific gene expression activity.
• 5.5. The intranuclear ionic environment is difficult to measure in an exact way. It can be influenced in a number of ways. The location of a gene, as determined by the position of the nucleus in the cytoplasm and by the association of chromatin to the nuclear matrix may be especially important in cells which can generate some type of intracellular gradient or in excitable cells.
• 6.6. In some somatic cell types—germinal vesicles may behave differently—the intranuclear inorganic ionic “environment” has been reported to be distinct from the cytoplasmic one. This challenges the widespread assumption that the nuclear envelope is always freely permeable to small molecules and inorganic ions.
• 7.7. It can be expected that the fast progress in the cloning of “electrically” controlled genes, in the identification of trans-acting factors, in their mode of interaction with genes and in the precise localization of genes within the nucleus may soon lead to substantial progress in this domain.