scholarly journals The Saccharomyces cerevisiae Start-specific transcription factor Swi4 interacts through the ankyrin repeats with the mitotic Clb2/Cdc28 kinase and through its conserved carboxy terminus with Swi6.

1996 ◽  
Vol 16 (6) ◽  
pp. 2647-2655 ◽  
Author(s):  
R F Siegmund ◽  
K A Nasmyth
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Transcriptional Activity ◽  
S Phase ◽  
Ankyrin Repeats ◽  
Carboxy Terminus ◽  
Specific Transcription Factor ◽  
Binding Factor ◽  
Cdc28 Kinase ◽  
Cyclin Genes

At a point in late G1 termed Start, yeast cells enter S phase, duplicate their spindle pole bodies, and form buds. These events require activation of Cdc28 kinase by G1 cyclins. Swi4 associates with Swi6 to form the SCB-binding factor complex which activates G1 cyclin genes CLN1 and CLN2 in late G1. In G2 and M phases, the transcriptional activity of SCB-binding factor is repressed by the mitotic Clb2/Cdc28 kinase. Mbp1, a transcription factor related to Swi4, forms the MCB-binding factor complex with Swi6, which activates DNA synthesis genes and S-phase cyclin genes CLB5 and CLB6 in late G1. Clb2/Cdc28 kinase is not required for the repression of MCB-binding factor transcriptional activity in G2 and M phase. We show here that the Swi4 carboxy terminus is sufficient for interaction with Swi6 in vitro. A carboxy-terminal domain of Swi6 is required and sufficient for interaction with Swi4. The carboxy terminus of Mbp1 is sufficient for interaction with Swi6, and the carboxy terminus of Swi6 is required for interaction with Mbp1. By coimmunoprecipitation, we show that Swi4 but not Mbp1 interacts with Clb2/Cdc28 kinase in vivo during the G2 and M phases of the cell cycle. We demonstrate that the ankyrin repeats of Swi4 mediate the interaction with Clb2/Cdc28 kinase. The ankyrin repeats constitute a domain by which a cell cycle-specific transcription factor can interact with cyclin-dependent kinase complexes, thus enabling it to link its transcriptional activity to cell cycle progression.

C/EBPϵ interacts with retinoblastoma and E2F1 during granulopoiesis

Blood ◽  
2004 ◽  
Vol 103 (3) ◽  
pp. 828-835 ◽  
Author(s):  
Sigal Gery ◽  
Adrian F. Gombart ◽  
Yuen K. Fung ◽  
H. Phillip Koeffler
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Broad Spectrum ◽  
Transcriptional Activity ◽  
Myeloid Cells ◽  
Cell Cycle Regulators ◽  
Granulocytic Differentiation ◽  
Specific Transcription Factor ◽  
Enhancer Binding Protein ◽  
Reporter Assays

AbstractCCAAT enhancer binding protein epsilon (C/EBPϵ) is a myeloid specific transcription factor that is essential for terminal granulocytic differentiation. Retinoblastoma (Rb) and E2F1 are critical cell cycle regulators that also have been implicated in several differentiation systems. Here, we demonstrate that C/EBPϵ interacts with Rb and E2F1 during granulocytic differentiation in NB4 and U937 human myeloid cells and in 32Dcl3 murine myeloid precursor cells. The interaction between C/EBPϵ and Rb enhances C/EBPϵ-mediated transcription of myeloid specific genes both in reporter assays and endogenously. The C/EBPϵ-E2F1 interaction results in repression of E2F1-mediated transcriptional activity. Finally, overexpression of C/EBPϵ in human myeloid cells leads to down-regulation of c-Myc. We propose that the interactions between C/EBPϵ, a tissue-specific transcription factor, and the broad-spectrum proteins, Rb and E2F1, are important in C/EBPϵ-induced terminal granulocytic differentiation.

scholarly journals The Transcription Factor B-Myb Is Maintained in an Inhibited State in Target Cells through Its Interaction with the Nuclear Corepressors N-CoR and SMRT

2002 ◽  
Vol 22 (11) ◽  
pp. 3663-3673 ◽  
Author(s):  
Xiaolin Li ◽  
Donald P. McDonnell
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Transcriptional Activity ◽  
Cyclin A ◽  
Myb Transcription Factor ◽  
Target Cells ◽  
Expression Of Genes ◽  
Phosphorylation Event ◽  
Cycle Regulation ◽  
Nuclear Corepressors

ABSTRACT The B-Myb transcription factor has been implicated in coordinating the expression of genes involved in cell cycle regulation. Although it is expressed in a ubiquitous manner, its transcriptional activity is repressed until the G1-S phase of the cell cycle by an unknown mechanism. In this study we used biochemical and cell-based assays to demonstrate that the nuclear receptor corepressors N-CoR and SMRT interact with B-Myb. The significance of these B-Myb-corepressor interactions was confirmed by the finding that B-Myb mutants, which were unable to bind N-CoR, exhibited constitutive transcriptional activity. It has been shown previously that phosphorylation of B-Myb by cdk2/cyclin A enhances its transcriptional activity. We have now determined that phosphorylation by cdk2/cyclin A blocks the interaction between B-Myb and N-CoR and that mutation of the corepressor binding site within B-Myb bypasses the requirement for this phosphorylation event. Cumulatively, these findings suggest that the nuclear corepressors N-CoR and SMRT serve a previously unappreciated role as regulators of B-Myb transcriptional activity.

scholarly journals The p110 Isoform of the CDP/Cux Transcription Factor Accelerates Entry into S Phase

2006 ◽  
Vol 26 (6) ◽  
pp. 2441-2455 ◽  
Author(s):  
Laurent Sansregret ◽  
Brigitte Goulet ◽  
Ryoko Harada ◽  
Brian Wilson ◽  
Lam Leduy ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Proteolytic Processing ◽  
Experimental Conditions ◽  
Division Rate ◽  
Cycle Progression ◽  
Processing Event

ABSTRACT The CDP/Cux transcription factor was previously found to acquire distinct DNA binding and transcriptional properties following a proteolytic processing event that takes place at the G1/S transition of the cell cycle. In the present study, we have investigated the role of the CDP/Cux processed isoform, p110, in cell cycle progression. Populations of cells stably expressing p110 CDP/Cux displayed a faster division rate and reached higher saturation density than control cells carrying the empty vector. p110 CDP/Cux cells reached the next S phase faster than control cells under various experimental conditions: following cell synchronization in G0 by growth factor deprivation, synchronization in S phase by double thymidine block treatment, or enrichment in G2 by centrifugal elutriation. In each case, duration of the G1 phase was shortened by 2 to 4 h. Gene inactivation confirmed the role of CDP/Cux as an accelerator of cell cycle progression, since mouse embryo fibroblasts obtained from Cutl1z/z mutant mice displayed a longer G1 phase and proliferated more slowly than their wild-type counterparts. The delay to enter S phase persisted following immortalization by the 3T3 protocol and transformation with H-RasV12. Moreover, CDP/Cux inactivation hindered both the formation of foci on a monolayer and tumor growth in mice. At the molecular level, expression of both cyclin E2 and A2 was increased in the presence of p110 CDP/Cux and decreased in its absence. Overall, these results establish that p110 CDP/Cux functions as a cell cycle regulator that accelerates entry into S phase.

Constitutive expression of the E2F1 transcription factor in fibroblasts alters G0 and S phase transit following serum stimulation

1996 ◽  
Vol 74 (1) ◽  
pp. 21-28 ◽  
Author(s):  
Thomas J. Logan ◽  
Kelly L. Jordan ◽  
David J. Hall
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Cell Lines ◽  
Constitutive Expression ◽  
S Phase ◽  
G1 Phase ◽  
Serum Starvation ◽  
Serum Stimulation ◽  
G0 Phase ◽  
E2f1 Transcription Factor

The E2F1 transcription factor was constitutively expressed in NIH3T3 fibroblasts to determine its effect on the cell cycle. These E2F1 cell lines were not tightly synchronized in G0 phase of the cell cycle following serum starvation, as are normal fibroblasts. Instead, the cells are spread throughout G0 and G1 phase with a portion of the population initiating DNA synthesis. Upon serum stimulation, the remaining cells in G0/G1 begin to enter S phase immediately but with a reduced rate. Constitutive expression of E2F1 appears to primarily affect the G0 phase, since transit of proliferating E2F1 cell lines through G1 phase is the same as control cells. Consistent with a shortened G0 phase, the E2F1 cell lines have a significantly reduced cellular volume. Additionally, the first S phase after serum stimulation, but not subsequent S phases, is nearly doubled in the E2F1 cell lines compared with control cells. Cell lines expressing a deletion mutant of E2F1 (termed E2F1d87), known to significantly affect cell shape, have cell cycle and volume characteristics similar to the E2F1 expressing cells. However, all S phase durations are considerably lengthened and the cells demonstrate delayed growth after plating.Key words: cell cycle, E2F1 transcription factor, G0/G1 phase.

Cell cycle-regulated transcription in fission yeast

2004 ◽  
Vol 32 (6) ◽  
pp. 967-972 ◽  
Author(s):  
C.J. McInerny
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Transcription Factor ◽  
Fission Yeast ◽  
Model Organism ◽  
Alternative Form ◽  
Regulation Of Transcription ◽  
Transcription Control ◽  
Binding Factor ◽  
Transcription Factor Complex

A fundamental process in biology is the mechanism by which cells duplicate and divide to produce two identical daughter cells. The fission yeast, Schizosaccharomyces pombe, has proved to be an excellent model organism to study the role that gene expression plays in this process. The basic paradigm emerging is that a number of groups of genes are expressed in successive waves at different cell cycle times. Transcription of a particular group is controlled by a common DNA motif present in each gene's promoter, bound by a transcription factor complex. Each motif and transcription factor complex is specific to the time in the cell cycle when the group of genes is expressed. Examples of this are the MBF (MCB-binding factor)/MCB (MluI cell cycle box) system controlling gene expression at the start of S-phase, and PBF (PCB-binding factor)/PCB (Pombe cell cycle box) regulation of transcription at the end of mitosis. In some cases, these transcription control systems also operate during the alternative form of cell division, meiosis.

scholarly journals S-phase transcriptional buffering quantified on two different promoters

2018 ◽  
Vol 1 (5) ◽  
pp. e201800086 ◽  
Author(s):  
Sharon Yunger ◽  
Pinhas Kafri ◽  
Liat Rosenfeld ◽  
Eliraz Greenberg ◽  
Noa Kinor ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcriptional Activity ◽  
Single Cells ◽  
Single Gene ◽  
Cell System ◽  
S Phase ◽  
Mrna Transcription ◽  
A Cell ◽  
Quantitative Fluorescence

Imaging of transcription by quantitative fluorescence-based techniques allows the examination of gene expression kinetics in single cells. Using a cell system for the in vivo visualization of mammalian mRNA transcriptional kinetics at single-gene resolution during the cell cycle, we previously demonstrated a reduction in transcription levels after replication. This phenomenon has been described as a homeostasis mechanism that buffers mRNA transcription levels with respect to the cell cycle stage and the number of transcribing alleles. Here, we examined how transcriptional buffering enforced during S phase affects two different promoters, the cytomegalovirus promoter versus the cyclin D1 promoter, that drive the same gene body. We found that global modulation of histone modifications could completely revert the transcription down-regulation imposed during replication. Furthermore, measuring these levels of transcriptional activity in fixed and living cells showed that the transcriptional potential of the genes was significantly higher than actual transcription levels, suggesting that promoters might normally be limited from reaching their full transcriptional potential.

scholarly journals Transcriptional Regulation in the G1-S Cell Cycle Stage in Fungi: Insights through Computational Analysis

2012 ◽  
Vol 6 (1) ◽  
pp. 43-54
Author(s):  
Viktor Martyanov ◽  
Robert H. Gross
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Dna Sequences ◽  
Binding Sites ◽  
Positional Distribution ◽  
Upstream Sequence ◽  
Regulatory Pathways ◽  
Binding Factor

The transcription factor complexes Mlu1-box binding factor (MBF) and Swi4/6 cell cycle box binding factor (SBF) regulate the cell cycle in Saccharomyces cerevisiae. They activate hundreds of genes and are responsible for nor-mal cell cycle progression from G1 to S phase. We investigated the conservation of MBF and SBF binding sites during fungal evolution. Orthologs of S. cerevisiae targets of these transcription factors were identified in 37 fungal species and their upstream regions were analyzed for putative transcription factor binding sites. Both groups displayed enrichment in specific putative regulatory DNA sequences in their upstream regions and showed different preferred upstream motif loca-tions, variable patterns of evolutionary conservation of the motifs and enrichment in unique biological functions for the regulated genes. The results indicate that despite high sequence similarity of upstream DNA motifs putatively associated with G1-S transcriptional regulation by MBF and SBF transcription factors, there are important upstream sequence feature differences that may help differentiate the two seemingly similar regulatory modes. The incorporation of upstream motif sequence comparison, positional distribution and evolutionary variability of the motif can complement functional infor-mation about roles of the respective gene products and help elucidate transcriptional regulatory pathways and functions.

The ZF87/MAZ transcription factor functions as a growth suppressor in fibroblasts

2000 ◽  
Vol 78 (4) ◽  
pp. 477-485 ◽  
Author(s):  
Matthew C Stubbs ◽  
InSung Min ◽  
Marc W Izzo ◽  
Ravikumar Rallapalli ◽  
Assia Derfoul ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Slow Growth ◽  
Chemotherapeutic Agent ◽  
S Phase ◽  
G1 Arrest ◽  
Zinc Finger Transcription Factor ◽  
Protein Levels ◽  
Myc Gene ◽  
Growth Suppressor

ZF87/MAZ is a zinc finger transcription factor that activates expression of tissue-specific genes and represses expression of the c-myc proto-oncogene. Infection of NIH3T3 fibroblasts with a retrovirus expressing ZF87/MAZ leads to a significant reduction in G418-resistant colonies, compared to cells infected with a retroviral control. Further, only a small fraction of the G418-resistant colonies express ZF87/MAZ. When the ZF87/MAZ-expressing colonies are expanded, they demonstrate a slow growth phenotype, a delayed transit through G1 phase and a decrease in endogenous c-myc gene expression and cyclin A and cyclin E protein levels. Consistent with a partial G1 arrest, the ZF87/MAZ-expressing cells show a reduced sensitivity to the S phase specific chemotherapeutic agent camptothecin. These data indicate that ZF87/MAZ is a growth suppressor protein in nontransformed cells, in part, by affecting the levels of key cell cycle regulatory proteins.Key words: cell cycle, ZF87/MAZ, cancer.

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