Derepression Of Gene Expression Research Articles

The key role of a basic domain of histone H2B N-terminal tail in the action of 5-bromodeoxyuridine to induce cellular senescence.

5-Bromodeoxyuridine (BrdU), a thymidine analogue, is an interesting reagent that modulates various biological phenomena. BrdU, upon incorporation into DNA, causes destabilized nucleosome positioning which leads to changes in heterochromatin organization and gene expression in cells. We have previously shown that BrdU effectively induces cellular senescence, a phenomenon of irreversible growth arrest in mammalian cells. Identification of the mechanism of action of BrdU would provide a novel insight into the molecular mechanisms of cellular senescence. Here, we showed that a basic domain in the histone H2B N-terminal tail, termed the HBR (histone H2B repression) domain, is involved in the action of BrdU. Notably, deletion of the HBR domain causes destabilized nucleosome positioning and derepression of gene expression, as does BrdU. We also showed that the genes up-regulated by BrdU significantly overlapped with those by deletion of the HBR domain, the result of which suggested that BrdU and deletion of the HBR domain act in a similar way. Furthermore, we showed that decreased HBR domain function induced cellular senescence or facilitated the induction of cellular senescence. These findings indicated that the HBR domain is crucially involved in the action of BrdU, and also suggested that disordered nucleosome organization may be involved in the induction of cellular senescence.

Repression and De-repression of Gene Expression in the Plant Immune Response: The Complexity of Modulation by Ca2+ and Calmodulin

Recent reports demonstrate a role of calmodulin (CaM)-binding DNA-binding proteins (transcription factors [TFs]) as repressors of the plant immune response through their interactions with promoters of a number of target genes. However, the role of Ca2+ in gene repression has not been tested. Thus, to infer the function of such TFs as repressors of transcription prior to pathogen attack raises questions about the role of Ca2+ in this transcription repression and subsequently in de-repression upon pathogen attack.

Transcriptional regulation of nonfermentable carbon utilization in budding yeast

Saccharomyces cerevisiae preferentially uses glucose as a carbon source, but following its depletion, it can utilize a wide variety of other carbons including nonfermentable compounds such as ethanol. A shift to a nonfermentable carbon source results in massive reprogramming of gene expression including genes involved in gluconeogenesis, the glyoxylate cycle, and the tricarboxylic acid cycle. This review is aimed at describing the recent progress made toward understanding the mechanism of transcriptional regulation of genes responsible for utilization of nonfermentable carbon sources. A central player for the use of nonfermentable carbons is the Snf1 kinase, which becomes activated under low glucose levels. Snf1 phosphorylates various targets including the transcriptional repressor Mig1, resulting in its inactivation allowing derepression of gene expression. For example, the expression of CAT8, encoding a member of the zinc cluster family of transcriptional regulators, is then no longer repressed by Mig1. Cat8 becomes activated through phosphorylation by Snf1, allowing upregulation of the zinc cluster gene SIP4. These regulators control the expression of various genes including those involved in gluconeogenesis. Recent data show that another zinc cluster protein, Rds2, plays a key role in regulating genes involved in gluconeogenesis and the glyoxylate pathway. Finally, the role of additional regulators such as Adr1, Ert1, Oaf1, and Pip2 is also discussed.

Cloning and Characterization of the EAP30 Subunit of the ELL Complex That Confers Derepression of Transcription by RNA Polymerase II

The product of the human oncogene ELL encodes an RNA polymerase II transcription factor that undergoes frequent translocation in acute myeloid leukemia (AML). In addition to its elongation activity, ELL contains a novel type of RNA polymerase II interaction domain that is capable of repressing polymerase activity in promoter-specific transcription. Remarkably, the ELL translocation that is found in patients with AML results in the deletion of exactly this functional domain. Here we report that the EAP30 subunit of the ELL complex has sequence homology to the Saccharomyces cerevisiae SNF8, whose genetic analysis suggests its involvement in the derepression of gene expression. Remarkably, EAP30 can interact with ELL and derepress ELL's inhibitory activity in vitro. This finding may reveal a key role for EAP30 in the pathogenesis of human leukemia.

A cell cycle role for a plant sucrose nonfermenting-1-related protein kinase (SnRK1) is indicated by expression in yeast

Plant sucrose nonfermenting-1 (SNF1)-related protein kinases (SnRK1s) have been shown to restore carbon catabolite derepression of gene expression in the yeast Saccharomyces cerevisiae when expressed in snf1 mutants. SNF1 has been implicated in the mediation of cell cycle control in response to nutrient levels and, in the present study, we show that expression of the rye (Secale cereale) SnRK1, RKIN1, in a yeast snf1 mutant has a dramatic effect on the size of cells growing on a minimal medium where SNF1 function is essential. The mean volume of the yeast cells which were expressing RKIN1 was two-thirds that of the whi1 mutant, the smallest viable cells known in S. cerevisiae, and the cells died after 3 days unless rescued onto complex medium. This is the first experimental evidence of a role for SnRK1s in plant cell cycle control.

Induction of Interferon in Lymphoblastoid Cell Lines

SummaryLymphoblastoid cell lines derived from normal individuals and from patients with a variety of myelo- and lym-phoproliferative disease states were examined for spontaneous interferon production. Interferon was synthesized by 17 of 21 lines investigated. No correlation was found with the disease state, and cultures from normal individuals produced interferon. Interferon production by lymphoblastoid cell lines is not correlated with infection of the cultures by EBV. The other nonviral inducers of interferon were studied and excluded as being responsible for the spontaneous production. It is proposed that interferon production by these cell lines is the result of a derepression of gene expression associated with the lymphoblastoid state analogous to interferon synthesis induced by lymphocyte mitogens.The senior author is grateful to several investigators for helpful discussions during the course of this work: to Drs. M. A. Fink, and M. Goldman, immunofluorescence of EBV; Drs. J. A. Rose, K. Berns, and ...