Threshold phenomena and long-distance activation of transcription by RNA polymerase II

Science ◽  
1992 ◽  
Vol 257 (5077) ◽  
pp. 1682-1685 ◽  
Author(s):  
P. Laybourn ◽  
J. Kadonaga
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Long Distance ◽  
Threshold Phenomena ◽  
Activation Of Transcription

RNA polymerase II cofactor PC2 facilitates activation of transcription by GAL4-AH in vitro

1994 ◽  
Vol 14 (6) ◽  
pp. 3927-3937
Author(s):  
M Kretzschmar ◽  
G Stelzer ◽  
R G Roeder ◽  
M Meisterernst
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Transcriptional Activation ◽  
Activation Domains ◽  
Positive Effects ◽  
Activation Of Transcription ◽  
Transcriptional Activation Domains ◽  
Necessary And Sufficient ◽  
Specific Pathway

We have isolated from a crude Hela cell cofactor fraction (USA) a novel positive cofactor that cooperates with the general transcription machinery to effect efficient stimulation of transcription by GAL4-AH, a derivative of the Saccharomyces cerevisiae regulatory factor GAL4. PC2 was shown to be a 500-kDa protein complex and to be functionally and biochemically distinct from native TFIID and previously identified cofactors. In the presence of native TFIID and other general factors, PC2 was necessary and sufficient for activation by GAL4-AH. Cofactor function was specific for transcriptional activation domains of GAL4-AH. The repressor histone H1 further potentiated but was not required for activation of transcription by GAL4-AH. On the basis of the observation that PC2 exerts entirely positive effects on transcription, we propose a model in which PC2 increases the activity of the preinitiation complex in the presence of an activator, thereby establishing a specific pathway during activation of RNA polymerase II.

scholarly journals Interaction between P-TEFb and the C-Terminal Domain of RNA Polymerase II Activates Transcriptional Elongation from Sites Upstream or Downstream of Target Genes

2002 ◽  
Vol 22 (1) ◽  
pp. 321-331 ◽  
Author(s):  
Ran Taube ◽  
Xin Lin ◽  
Dan Irwin ◽  
Koh Fujinaga ◽  
B. Matija Peterlin
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Target Genes ◽  
Elongation Factor ◽  
Transcriptional Elongation ◽  
Cyclin T1 ◽  
Positive Transcription Elongation Factor ◽  
Terminal Domain ◽  
Activation Of Transcription

ABSTRACT Transcriptional elongation by RNA polymerase II (RNAPII) is regulated by the positive transcription elongation factor b (P-TEFb). P-TEFb is composed of Cdk9 and C-type cyclin T1 (CycT1), CycT2a, CycT2b, or CycK. The role of the C-terminal region of CycT1 and CycT2 remains unknown. In this report, we demonstrate that these sequences are essential for the activation of transcription by P-TEFb via DNA, i.e., when CycT1 is tethered upstream or downstream of promoters and coding sequences. A histidine-rich stretch, which is conserved between CycT1 and CycT2 in this region, bound the C-terminal domain of RNAPII. This binding was required for the subsequent expression of full-length transcripts from target genes. Thus, P-TEFb could mediate effects of enhancers on the elongation of transcription.

scholarly journals A transcriptional mediator protein that is required for activation of many RNA polymerase II promoters and is conserved from yeast to humans.

1997 ◽  
Vol 17 (8) ◽  
pp. 4622-4632 ◽  
Author(s):  
Y C Lee ◽  
S Min ◽  
B S Gim ◽  
Y J Kim
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Transcriptional Activation ◽  
Mediator Complex ◽  
Temperature Sensitive ◽  
Yeast Saccharomyces Cerevisiae ◽  
Inducible Promoters ◽  
Activation Of Transcription

A temperature-sensitive mutation was obtained in Med6p, a component of the mediator complex from the yeast Saccharomyces cerevisiae. The mediator complex has been shown to enable transcriptional activation in vitro. This mutation in Med6p abolished activation of transcription from four of five inducible promoters tested in vivo. There was no effect, however, on uninduced transcription, transcription of constitutively expressed genes, or transcription by RNA polymerases I and III. Mediator-RNA polymerase II complex isolated from the mutant yeast strain was temperature sensitive for transcriptional activation in a reconstituted in vitro system due to a defect in initiation complex formation. A database search revealed the existence of MED6-related genes in humans and Caenorhabditis elegans, suggesting that the role of mediator in transcriptional activation is conserved throughout the evolution.

Long Distance Cyclin D1 Activation in B Cell Malignancies: Role of RNA Polymerase II.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1113-1113
Author(s):  
Hui Liu ◽  
Jin Wang ◽  
Richard T. Maziarz ◽  
Elliot M. Epner
Keyword(s):  
B Cells ◽  
Rna Polymerase ◽  
B Cell ◽  
Cyclin D1 ◽  
Rna Polymerase Ii ◽  
Gene Locus ◽  
Regulatory Elements ◽  
Long Distance ◽  
B Cell Malignancies ◽  
Pol Ii

Abstract Translocations involving the immunoglobulin heavy chain gene locus (IgH) are common in B cell malignancies. One common target gene is cyclin D1, which is deregulated in most patients with mantle cell lymphoma (MCL) and approximately 15–20% of patients with multiple myeloma (MM). Cyclin D1 is not expressed in normal lymphocytes; cyclin D1 expression in B cell malignancies is deregulated by IgH translocations and insertions. We have shown that the cyclin D1 locus, including the promoter and upstream regions, are acetylated and DNA hypomethylated in both malignant and nonmalignant B cells (Liu et al, Blood in press). Using chromatin immunoprecipitation (ChIP) assays, we have found that RNA polymerase II (Pol II) is a) present at the cyclin D1 promoter b) located at regions far upstream of the cyclin D1 gene and c) present at 3′ Cα IgH regulatory elements only in cyclin D1 expressing malignant B cells. Pol II is present at the translocation breakpoint in a MCL cell line, but we do not find Pol II present continuously from the IgH regulatory regions to the cyclin D1 promoter. Confirmatory RT-PCR analyses also do not demonstrate continous evidence of RNA transcripts extending from the IgH regulatory elements to the cyclin D1 promoter. Mutants derived from gene targeting experiments that have lost the translocated chromosome show Pol II binding only at the Eu intronic enhancer, consistent with known promoter acivity and sterile transcripts originating at this location. Our data suggest that Pol II may play a important role in initiating long distance cyclin D1 deregulation by translocated IgH sequences. Analogous to the mouse β-globin gene locus, a polymerase transfer (LPT) model may be invoked, where other proteins such as CTCF effect Pol II transfer from 3′ Cα IgH regulatory sequences to the cyclin D1 promoter and initiate cyclin D1 transcription.

scholarly journals Requirement for a Functional Interaction between Mediator Components Med6 and Srb4 in RNA Polymerase II Transcription

1998 ◽  
Vol 18 (9) ◽  
pp. 5364-5370 ◽  
Author(s):  
Young Chul Lee ◽  
Young-Joon Kim
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Functional Relationship ◽  
Specific Interaction ◽  
Class Ii ◽  
Temperature Sensitive ◽  
Functional Interaction ◽  
Activation Of Transcription ◽  
Allele Specific ◽  
Rna Polymerase Ii Holoenzyme

ABSTRACT Regulated transcription of class II genes of the yeastSaccharomyces cerevisiae requires the diverse functions of mediator complex. In particular, MED6 is essential for activated transcription from many class II promoters, suggesting that it functions as a key player in the relay of activator signals to the basal transcription machinery. To identify the functional relationship between MED6 and other transcriptional regulators, we conducted a genetic screen to isolate a suppressor of a temperature-sensitive (ts) med6 mutation. We identified an SRB4 allele as a dominant and allele-specific suppressor of med6-ts. A single missense mutation inSRB4 can specifically suppress transcriptional defects caused by the med6 ts mutation, indicating a functional interaction between these two mediator subunits in the activation of transcription. Biochemical analysis of mediator subassembly revealed that mediator can be dissociated into two tightly associated subcomplexes. The Med6 and Srb4 proteins are contained in the same subcomplex together with other dominant Srb proteins, consistent with their functional relationship revealed by the genetic study. Our results suggest not only the existence of a specific interaction between Med6 and Srb4 but also the requirement of this interaction in transcriptional regulation of RNA polymerase II holoenzyme.

scholarly journals Localization of the glucocorticoid receptor in discrete clusters in the cell nucleus

1995 ◽  
Vol 108 (9) ◽  
pp. 3003-3011 ◽  
Author(s):  
B. van Steensel ◽  
M. Brink ◽  
K. van der Meulen ◽  
E.P. van Binnendijk ◽  
D.G. Wansink ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Cell Nucleus ◽  
Glucocorticoid Receptors ◽  
Cell Types ◽  
Activation Of Transcription ◽  
Discrete Domains ◽  
Receptor Clusters ◽  
Antagonist Ru486

The cell nucleus is highly organized. Many nuclear functions are localized in discrete domains, suggesting that compartmentalization is an important aspect of the regulation and coordination of nuclear functions. We investigated the subnuclear distribution of the glucocorticoid receptor, a hormone-dependent transcription factor. By immunofluorescent labeling and confocal microscopy we found that after stimulation with the agonist dexamethasone the glucocorticoid receptor is concentrated in 1,000-2,000 clusters in the nucleoplasm. This distribution was observed in several cell types and with three different antibodies against the glucocorticoid receptor. A similar subnuclear distribution of glucocorticoid receptors was found after treatment of cells with the antagonist RU486, suggesting that the association of the glucocorticoid receptor in clusters does not require transformation of the receptor to a state that is able to activate transcription. By dual labeling we found that most dexamethasone-induced receptor clusters do not colocalize with sites of pre-mRNA synthesis. We also show that RNA polymerase II is localized in a large number of clusters in the nucleus. Glucocorticoid receptor clusters did not significantly colocalize with these RNA polymerase II clusters or with domains containing the splicing factor SC-35. Taken together, these results suggest that most clustered glucocorticoid receptor molecules are not directly involved in activation of transcription.

scholarly journals RNA polymerase II cofactor PC2 facilitates activation of transcription by GAL4-AH in vitro.

1994 ◽  
Vol 14 (6) ◽  
pp. 3927-3937 ◽  
Author(s):  
M Kretzschmar ◽  
G Stelzer ◽  
R G Roeder ◽  
M Meisterernst
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Transcriptional Activation ◽  
Activation Domains ◽  
Positive Effects ◽  
Activation Of Transcription ◽  
Transcriptional Activation Domains ◽  
Necessary And Sufficient ◽  
Specific Pathway

We have isolated from a crude Hela cell cofactor fraction (USA) a novel positive cofactor that cooperates with the general transcription machinery to effect efficient stimulation of transcription by GAL4-AH, a derivative of the Saccharomyces cerevisiae regulatory factor GAL4. PC2 was shown to be a 500-kDa protein complex and to be functionally and biochemically distinct from native TFIID and previously identified cofactors. In the presence of native TFIID and other general factors, PC2 was necessary and sufficient for activation by GAL4-AH. Cofactor function was specific for transcriptional activation domains of GAL4-AH. The repressor histone H1 further potentiated but was not required for activation of transcription by GAL4-AH. On the basis of the observation that PC2 exerts entirely positive effects on transcription, we propose a model in which PC2 increases the activity of the preinitiation complex in the presence of an activator, thereby establishing a specific pathway during activation of RNA polymerase II.

Cyclin D1 activation in B-cell malignancy: association with changes in histone acetylation, DNA methylation, and RNA polymerase II binding to both promoter and distal sequences

Blood ◽  
2004 ◽  
Vol 104 (8) ◽  
pp. 2505-2513 ◽  
Author(s):  
Hui Liu ◽  
Jin Wang ◽  
Elliot M. Epner
Keyword(s):  
Dna Methylation ◽  
Rna Polymerase ◽  
B Cell ◽  
Cyclin D1 ◽  
Histone Acetylation ◽  
Rna Polymerase Ii ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Regulatory Sequences ◽  
Long Distance

Abstract Cyclin D1 expression is deregulated by chromosome translocation in mantle cell lymphoma and a subset of multiple myeloma. The molecular mechanisms involved in long-distance gene deregulation remain obscure, although changes in acetylated histones and methylated CpG dinucleotides may be important. The patterns of DNA methylation and histone acetylation were determined at the cyclin D1 locus on chromosome 11q13 in B-cell malignancies. The cyclin D1 promoter was hypomethylated and hyperacetylated in expressing cell lines and patient samples, and methylated and hypoacetylated in nonexpressing cell lines. Domains of hyperacetylated histones and hypomethylated DNA extended over 120 kb upstream of the cyclin D1 gene. Interestingly, hypomethylated DNA and hyperacetylated histones were also located at the cyclin D1 promoter but not the upstream major translocation cluster region in cyclin D1-nonexpressing, nontumorigenic B and T cells. RNA polymerase II binding was demonstrated both at the cyclin D1 promoter and 3′ immunoglobulin heavy-chain regulatory regions only in malignant B-cell lines with deregulated cyclin D1 expression. Our results suggest a model where RNA polymerase II bound at IgH regulatory sequences can activate the cyclin D1 promoter by either long-range polymerase transfer or tracking.

Nutrient-regulated gene expression in eukaryotes

2006 ◽  
Vol 73 ◽  
pp. 85-96 ◽  
Author(s):  
Richard J. Reece ◽  
Laila Beynon ◽  
Stacey Holden ◽  
Amanda D. Hughes ◽  
Karine Rébora ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Transcriptional Control ◽  
Direct Interaction ◽  
Signalling Pathways ◽  
A Cell ◽  
One Step ◽  
Higher Eukaryotes ◽  
Regulated Gene Expression

The recognition of changes in environmental conditions, and the ability to adapt to these changes, is essential for the viability of cells. There are numerous well characterized systems by which the presence or absence of an individual metabolite may be recognized by a cell. However, the recognition of a metabolite is just one step in a process that often results in changes in the expression of whole sets of genes required to respond to that metabolite. In higher eukaryotes, the signalling pathway between metabolite recognition and transcriptional control can be complex. Recent evidence from the relatively simple eukaryote yeast suggests that complex signalling pathways may be circumvented through the direct interaction between individual metabolites and regulators of RNA polymerase II-mediated transcription. Biochemical and structural analyses are beginning to unravel these elegant genetic control elements.

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