scholarly journals Bromodomain analysis of Brd2-dependent transcriptional activation of cyclin A1

2005 ◽  
Vol 387 (1) ◽  
pp. 257-269 ◽  
Author(s):  
Anupama SINHA ◽  
Douglas V. FALLER ◽  
Gerald V. DENIS
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Transcriptional Activation ◽  
Transcriptional Repression ◽  
Cyclin A ◽  
S Phase ◽  
Histone H4 ◽  
Transcription Control ◽  
Histone H4 Acetylation ◽  
E2f Transcription Factors

Cyclin A is regulated primarily through transcription control during the mammalian cell cycle. A dual mechanism of cyclin A transcriptional repression involves, on the one hand, promoter-bound inhibitory complexes of E2F transcription factors and RB (retinoblastoma) family proteins, and on the other, chromatin-directed histone deacetylase activity that is recruited to the cyclin A promoter early in the cell cycle in association with these RB proteins. This dual regulation maintains transcriptional silence of the cyclin A locus until its transcription is required in S-phase. At that time, RB family members dissociate from E2F proteins and nucleosomal restructuring of the locus takes place, to permit transcriptional activation and resultant S-phase progression to proceed. We have identified a double bromo-domain-containing protein Brd2, which exhibits apparent ‘scaffold’ or transcriptional adapter functions and mediates recruitment of both E2F transcription factors and chromatin-remodelling activity to the cyclin A promoter. We have shown previously that Brd2-containing nuclear, multiprotein complexes contain E2F-1 and -2. In the present study, we show that, in S-phase, they also contain histone H4-directed acetylase activity. Overexpression of Brd2 in fibroblasts accelerates the cell cycle through increased expression of cyclin A and its associated cyclin-dependent kinase activity. Chromatin immunoprecipitation studies show that Brd2 is physically present at the cyclin A promoter and its overexpression promotes increased histone H4 acetylation at the promoter as it becomes transcriptionally active, suggesting a new model for the dual regulation of cyclin A.

scholarly journals Activation of the G2/M-Specific Gene CLB2 Requires Multiple Cell Cycle Signals

2007 ◽  
Vol 27 (23) ◽  
pp. 8364-8373 ◽  
Author(s):  
J. Veis ◽  
H. Klug ◽  
M. Koranda ◽  
G. Ammerer
Keyword(s):  
Cell Cycle ◽  
Transcriptional Activation ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Specific Gene ◽  
Histone H4 ◽  
Cycle Progression ◽  
Histone H4 Acetylation ◽  
Multiple Cell

ABSTRACT In budding yeast (Saccharomyces cerevisiae), the periodic expression of the G2/M-specific gene CLB2 depends on a DNA binding complex that mediates its repression during G1 and activation from the S phase to the exit of mitosis. The switch from low to high expression levels depends on the transcriptional activator Ndd1. We show that the inactivation of the Sin3 histone deacetylase complex bypasses the essential role of Ndd1 in cell cycle progression. Sin3 and its catalytic subunit Rpd3 associate with the CLB2 promoter during the G1 phase of the cell cycle. Both proteins dissociate from the promoter at the onset of the S phase and reassociate during G2 phase. Sin3 removal coincides with a transient increase in histone H4 acetylation followed by the expulsion of at least one nucleosome from the promoter region. Whereas the first step depends on Cdc28/Cln1 activity, Ndd1 function is required for the second step. Since the removal of Sin3 is independent of Ndd1 recruitment and Cdc28/Clb activity it represents a unique regulatory step which is distinct from transcriptional activation.

scholarly journals Homeostatic control of START through negative feedback between Cln3-Cdk1 and Rim15/Greatwall kinase in budding yeast

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Nicolas Talarek ◽  
Elisabeth Gueydon ◽  
Etienne Schwob
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Cell Size ◽  
Negative Feedback ◽  
S Phase ◽  
Homeostatic Control ◽  
Cell Cycle Entry ◽  
Greatwall Kinase ◽  
E2f Transcription Factors ◽  
Phase Entry

How cells coordinate growth and division is key for size homeostasis. Phosphorylation by G1-CDK of Whi5/Rb inhibitors of SBF/E2F transcription factors triggers irreversible S-phase entry in yeast and metazoans, but why this occurs at a given cell size is not fully understood. We show that the yeast Rim15-Igo1,2 pathway, orthologous to Gwl-Arpp19/ENSA, is up-regulated in early G1 and helps promoting START by preventing PP2ACdc55 to dephosphorylate Whi5. RIM15 overexpression lowers cell size while IGO1,2 deletion delays START in cells with low CDK activity. Deletion of WHI5, CDC55 and ectopic CLN2 expression suppress the START delay of igo1,2∆ cells. Rim15 activity increases after cells switch from fermentation to respiration, where Igo1,2 contribute to chromosome maintenance. Interestingly Cln3-Cdk1 also inhibits Rim15 activity, which enables homeostatic control of Whi5 phosphorylation and cell cycle entry. We propose that Rim15/Gwl regulation of PP2A plays a hitherto unappreciated role in cell size homeostasis during metabolic rewiring of the cell cycle.

scholarly journals Histone H4 acetylation during UV light induced G1and S phase arrest of the cell cycle

Cell Cycle ◽  
2008 ◽  
Vol 7 (10) ◽  
pp. 1496-1498 ◽  
Author(s):  
Miglena Koprinarova ◽  
George Russev
Keyword(s):  
Cell Cycle ◽  
Uv Light ◽  
S Phase ◽  
Histone H4 ◽  
Phase Arrest ◽  
Histone H4 Acetylation ◽  
S Phase Arrest

scholarly journals Epigenetics and cytoprotection with heat acclimation

2016 ◽  
Vol 120 (6) ◽  
pp. 702-710 ◽  
Author(s):  
Michal Horowitz
Keyword(s):  
Transcription Factors ◽  
Heat Shock ◽  
Transcriptional Activation ◽  
Chromatin Condensation ◽  
Heat Acclimation ◽  
Heat Shock Factor 1 ◽  
Epigenetic Mechanisms ◽  
Histone H4 ◽  
Cross Tolerance ◽  
Histone H4 Acetylation

Studying “phenotypic plasticity” involves comparison of traits expressed in response to environmental fluctuations and aims to understand tolerance and survival in new settings. Reversible phenotypic changes that enable individuals to match their phenotype to environmental demands throughout life can be artificially induced, i.e., acclimation or occur naturally, i.e., acclimatization. The onset and achievement of acclimatory homeostasis are determined by molecular programs that induce the acclimated transcriptome. In heat acclimation, much evidence suggests that epigenetic mechanisms are powerful players in these processes. Epigenetic mechanisms affect the accessibility of the DNA to transcription factors, thereby regulating gene expression and controlling the phenotype. The heat-acclimated phenotype confers cytoprotection against novel stressors via cross-tolerance mechanisms, by attenuation of the initial damage and/or by accelerating spontaneous recovery through the release of help signals. This indispensable acclimatory feature has a memory and can be rapidly reestablished after the loss of acclimation and the return to the physiological preacclimated phenotype. The transcriptional landscape of the deacclimated phenotype includes constitutive transcriptional activation of epigenetic bookmarks. Heat shock protein (HSP) 70/HSP90/heat shock factor 1 memory protocol demonstrated constitutive histone H4 acetylation on hsp70 and hsp90 promotors. Novel players in the heat acclimation setup are poly(ADP-ribose)ribose polymerase 1 affecting chromatin condensation, DNA linker histones from the histone H1 cluster, and transcription factors associated with the P38 pathway. We suggest that these orchestrated responses maintain euchromatin and proteostasis during deacclimation and predispose to rapid reacclimation and cytoprotection. These mechanisms represent within-life epigenetic adaptations and cytoprotective memory.

scholarly journals Plant D–type cyclins and the control of G1 progression

2002 ◽  
Vol 357 (1422) ◽  
pp. 749-760 ◽  
Author(s):  
E. Ann Oakenfull ◽  
Catherine Riou-Khamlichi ◽  
A. H. Murray
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
S Phase ◽  
G1 Phase ◽  
Basic Pattern ◽  
Rb Protein ◽  
E2f Transcription Factors ◽  
Rb Phosphorylation ◽  
Phase Entry ◽  
Plant Homologue

The basic pattern of controls that operate during the G1 phase of the plant cell cycle shows much closer similarity to animals than to the yeasts and other fungi. The activity of D–type cyclin (CycD) kinases is induced in response to stimulatory signals, and these phosphorylate the plant homologue of the retinoblastoma tumour susceptibility (Rb) protein. It is likely that Rb phosphorylation results in the activation of genes under the control of E2F transcription factors, including those required for S phase entry. As the initial triggers of the cascade, attention has focused on the CycDs, and a family of 10 genes is present in Arabidopsis , divided into three major and three minor groups. Analysis to date suggests that these groups are functionally distinct.

scholarly journals Identification of cell cycle–regulated genes periodically expressed in U2OS cells and their regulation by FOXM1 and E2F transcription factors

2013 ◽  
Vol 24 (23) ◽  
pp. 3634-3650 ◽  
Author(s):  
Gavin D. Grant ◽  
Lionel Brooks ◽  
Xiaoyang Zhang ◽  
J. Matthew Mahoney ◽  
Viktor Martyanov ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Cell Line ◽  
High Throughput Sequencing ◽  
S Phase ◽  
Luciferase Assay ◽  
Live Cells ◽  
Comprehensive Picture ◽  
E2f Transcription Factors ◽  
Unique Cell

We identify the cell cycle–regulated mRNA transcripts genome-wide in the osteosarcoma-derived U2OS cell line. This results in 2140 transcripts mapping to 1871 unique cell cycle–regulated genes that show periodic oscillations across multiple synchronous cell cycles. We identify genomic loci bound by the G2/M transcription factor FOXM1 by chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) and associate these with cell cycle–regulated genes. FOXM1 is bound to cell cycle–regulated genes with peak expression in both S phase and G2/M phases. We show that ChIP-seq genomic loci are responsive to FOXM1 using a real-time luciferase assay in live cells, showing that FOXM1 strongly activates promoters of G2/M phase genes and weakly activates those induced in S phase. Analysis of ChIP-seq data from a panel of cell cycle transcription factors (E2F1, E2F4, E2F6, and GABPA) from the Encyclopedia of DNA Elements and ChIP-seq data for the DREAM complex finds that a set of core cell cycle genes regulated in both U2OS and HeLa cells are bound by multiple cell cycle transcription factors. These data identify the cell cycle–regulated genes in a second cancer-derived cell line and provide a comprehensive picture of the transcriptional regulatory systems controlling periodic gene expression in the human cell division cycle.

The Role of Retinoblastoma Protein in Cell Cycle Regulation: An Updated Review

2021 ◽  
Vol 20 ◽  
Author(s):  
Rabih Roufayel ◽  
Rabih Mezher ◽  
Kenneth B. Storey
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Transcription Factors ◽  
Cell Cycle Control ◽  
Expression Of Genes ◽  
E2f Transcription Factor ◽  
Cellular Energetics ◽  
Development And Differentiation ◽  
E2f Transcription Factors ◽  
Rb Phosphorylation

: Selected transcription factors have critical roles to play in organism survival by regulating the expression of genes that control the adaptations needed to handle stress conditions. The retinoblastoma (Rb) protein coupled with the E2F transcription factor family was demonstrated to have roles in controlling the cell cycle during freezing and associated environmental stresses (anoxia, dehydration). Rb phosphorylation or acetylation at different sites provide a mechanism for repressing cell proliferation that is under the control of E2F transcription factors in animals facing stresses that disrupt cellular energetics or cell volume controls. Other central regulators of the cell cycle including Cyclins, Cyclin dependent kinases (Cdks), and checkpoint proteins detect DNA damage or any improper replication, blocking further progression of cell cycle and interrupting cell proliferation. This review provides an insight into the molecular regulatory mechanisms of cell cycle control, focusing on Rb-E2F along with Cyclin-Cdk complexes typically involved in development and differentiation that need to be regulated in order to survive extreme cellular stress.

scholarly journals RAE-1 ligands for the NKG2D receptor are regulated by E2F transcription factors, which control cell cycle entry

2012 ◽  
Vol 209 (13) ◽  
pp. 2409-2422 ◽  
Author(s):  
Heiyoun Jung ◽  
Benjamin Hsiung ◽  
Kathleen Pestal ◽  
Emily Procyk ◽  
David H. Raulet
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Stress Responses ◽  
Transcriptional Activation ◽  
Posttranscriptional Regulation ◽  
Cellular Proliferation ◽  
Control Cell ◽  
T Cell Subsets ◽  
Cell Cycle Entry

The NKG2D stimulatory receptor expressed by natural killer cells and T cell subsets recognizes cell surface ligands that are induced on transformed and infected cells and facilitate immune rejection of tumor cells. We demonstrate that expression of retinoic acid early inducible gene 1 (RAE-1) family NKG2D ligands in cancer cell lines and proliferating normal cells is coupled directly to cell cycle regulation. Raet1 genes are directly transcriptionally activated by E2F family transcription factors, which play a central role in regulating cell cycle entry. Induction of RAE-1 occurred in primary cell cultures, embryonic brain cells in vivo, and cells in healing skin wounds and, accordingly, wound healing was delayed in mice lacking NKG2D. Transcriptional activation by E2Fs is likely coordinated with posttranscriptional regulation by other stress responses. These findings suggest that cellular proliferation, as occurs in cancer cells but also other pathological conditions, is a key signal tied to immune reactions mediated by NKG2D-bearing lymphocytes.

scholarly journals The initiation and pattern of spread of histone H4 acetylation parallel the order of transcriptional activation of genes in the aflatoxin cluster

2007 ◽  
Vol 66 (3) ◽  
pp. 713-726 ◽  
Author(s):  
Ludmila V. Roze ◽  
Anna E. Arthur ◽  
Sung-Yong Hong ◽  
Anindya Chanda ◽  
John E. Linz
Keyword(s):  
Transcriptional Activation ◽  
Histone H4 ◽  
Histone H4 Acetylation
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