Cell cycle-regulated transcription in fission yeast

2004 ◽  
Vol 32 (6) ◽  
pp. 967-972 ◽  
Author(s):  
C.J. McInerny

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.

2000 ◽  
Vol 11 (10) ◽  
pp. 3411-3424 ◽  
Author(s):  
Sylvie Tournier ◽  
Jonathan B.A. Millar

Hyperactivation of Cdc2 in fission yeast causes cells to undergo a lethal premature mitosis called mitotic catastrophe. This phenotype is observed in cdc2-3w wee1-50 cells at high temperature. Eleven of 17 mutants that suppress this phenotype define a single complementation group, mcs1. The mcs1-77mutant also suppresses lethal inactivation of the Wee1 and Mik1 tyrosine kinases and thus delays mitosis independently of Cdc2 tyrosine phosphorylation. We have cloned mcs1 by isolating suppressors of the cell cycle arrest phenotype of mcs1-77 cdc25-22 cells and found that it encodes Res2, a component of the START gene–specific transcription factor complex MBF (also known as DSC-1). The mcs1-77 mutant bears a single point mutation in the DNA-binding domain of Res2 that causes glycine 68 to be replaced by a serine residue. Importantly, two substrates of the anaphase-promoting complex (APC), the major B-type cyclin, Cdc13, and the anaphase inhibitor, Cut2, are unstable in G2-phasemcs1-77 cells. Consistent with this, we observe abnormal sister chromatid separation in mcs1-77 cdc25-22 cells at the restrictive temperature. Mutation of either Cdc10 or Res1 also deregulates MBF-dependent transcription and causes a G2 delay. We find that this cell cycle delay is abolished in the absence of the APC regulator Ste9/Srw1 and that the periodic expression of Ste9/Srw1 is controlled by the MBF complex. These data suggest that in fission yeast the MBF complex plays a key role in the inactivation of cyclin B and Cut2 destruction by controlling the periodic production of APC regulators.


2021 ◽  
Vol 17 (10) ◽  
pp. e1009354
Author(s):  
Sergio Sarnataro ◽  
Andrea Riba ◽  
Nacho Molina

Proliferating cells experience a global reduction of transcription during mitosis, yet their cell identity is maintained and regulatory information is propagated from mother to daughter cells. Mitotic bookmarking by transcription factors has been proposed as a potential mechanism to ensure the reactivation of transcription at the proper set of genes exiting mitosis. Recently, mitotic transcription and waves of transcription reactivation have been observed in synchronized populations of human hepatoma cells. However, the study did not consider that mitotic-arrested cell populations progressively desynchronize leading to measurements of gene expression on a mixture of cells at different internal cell-cycle times. Moreover, it is not well understood yet what is the precise role of mitotic bookmarking on mitotic transcription as well as on the transcription reactivation waves. Ultimately, the core gene regulatory network driving the precise transcription reactivation dynamics remains to be identified. To address these questions, we developed a mathematical model to correct for the progressive desynchronization of cells and estimate gene expression dynamics with respect to a cell-cycle pseudotime. Furthermore, we used a multiple linear regression model to infer transcription factor activity dynamics. Our analysis allows us to characterize waves of transcription factor activities exiting mitosis and predict a core gene regulatory network responsible of the transcription reactivation dynamics. Moreover, we identified more than 60 transcription factors that are highly active during mitosis and represent new candidates of mitotic bookmarking factors which could be relevant therapeutic targets to control cell proliferation.


2005 ◽  
Vol 16 (6) ◽  
pp. 2734-2745 ◽  
Author(s):  
Karen M. Lee ◽  
Ida Miklos ◽  
Hongyan Du ◽  
Stephen Watt ◽  
Zsolt Szilagyi ◽  
...  

The fission yeast Mcs6–Mcs2–Pmh1 complex, homologous to metazoan Cdk7–cyclin H-Mat1, has dual functions in cell division and transcription: as a partially redundant cyclin-dependent kinase (CDK)-activating kinase (CAK) that phosphorylates the major cell cycle CDK, Cdc2, on Thr-167; and as the RNA polymerase (Pol) II carboxyl-terminal domain (CTD) kinase associated with transcription factor (TF) IIH. We analyzed conditional mutants of mcs6 and pmh1, which activate Cdc2 normally but cannot complete cell division at restrictive temperature and arrest with decreased CTD phosphorylation. Transcriptional profiling by microarray hybridization revealed only modest effects on global gene expression: a one-third reduction in a severe mcs6 mutant after prolonged incubation at 36°C. In contrast, a small subset of transcripts (∼5%) decreased by more than twofold after Mcs6 complex function was compromised. The signature of repressed genes overlapped significantly with those of cell separation mutants sep10 and sep15. Sep10, a component of the Pol II Mediator complex, becomes essential in mcs6 or pmh1 mutant backgrounds. Moreover, transcripts dependent on the forkhead transcription factor Sep1, which are expressed coordinately during mitosis, were repressed in Mcs6 complex mutants, and Mcs6 also interacts genetically with Sep1. Thus, the Mcs6 complex, a direct activator of Cdc2, also influences the cell cycle transcriptional program, possibly through its TFIIH-associated kinase function.


2020 ◽  
Author(s):  
Sergio Sarnataro ◽  
Andrea Riba ◽  
Nacho Molina

AbstractProliferating cells experience a global reduction of transcription during mitosis, yet their cell identity is maintained and regulatory information is propagated from mother to daughter cells. Mitotic bookmarking by transcription factors has been proposed as a potential mechanism to ensure the reactivation of transcription at the proper set of genes exiting mitosis. Recently, mitotic transcription and waves of transcription reactivation have been observed in synchronized populations of human hepatoma cells. However, the study did not consider that mitotic-arrested cell populations progressively desynchronize leading to measurements of gene expression on a mixture of cells at different internal cell-cycle times. Moreover, it is not well understood yet what is the precise role of mitotic bookmarking on mitotic transcription as well as on the transcription reactivation waves. Ultimately, the core gene regulatory network driving the precise transcription reactivation dynamics remains to be identified. To address these questions, we developed a mathematical model to correct for the progressive desynchronization of cells and estimate gene expression dynamics with respect to a cell-cycle pseudotime. Furthermore, we used a multiple linear regression model to infer transcription factor activity dynamics. Our analysis allows us to characterize waves of transcription factor activities exiting mitosis and identify a core gene regulatory network responsible of the transcription reactivation dynamics. Moreover, we identified more than 60 transcription factors that are highly active during mitosis and represent new candidates of mitotic bookmarking factors which could represent relevant therapeutic targets to control cell proliferation.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ra Ham Lee ◽  
Jae-Don Oh ◽  
Jae Sam Hwang ◽  
Hak-Kyo Lee ◽  
Donghyun Shin

AbstractMalignant melanoma is highly resistant to conventional treatments and is one of the most aggressive types of skin cancers. Conventional cancer treatments are limited due to drug resistance, tumor selectivity, and solubility. Therefore, new treatments with fewer side effects and excellent effects should be developed. In previous studies, we have analyzed antimicrobial peptides (AMPs), which showed antibacterial and anti-inflammatory effects in insects, and some AMPs also exhibited anticancer efficacy. Anticancer peptides (ACPs) are known to have fewer side effects and high anticancer efficacy. In this study, the insect-derived peptide poecilocorisin-1 (PCC-1) did not induce toxicity in the human epithelial cell line HaCaT, but its potential as an anticancer agent was confirmed through specific effects of antiproliferation, apoptosis, and cell cycle arrest in two melanoma cell lines, SK-MEL-28 and G361. Additionally, we discovered a novel anticancer mechanism of insect-derived peptides in melanoma through the regulation of transcription factor Sp1 protein, which is overexpressed in cancer, apoptosis, and cell cycle-related proteins. Taken together, this study aims to clarify the anticancer efficacy and safety of insect-derived peptides and to present their potential as future therapeutic agents.


PLoS ONE ◽  
2009 ◽  
Vol 4 (9) ◽  
pp. e7035 ◽  
Author(s):  
Emmanuelle Deniaud ◽  
Joël Baguet ◽  
Roxane Chalard ◽  
Bariza Blanquier ◽  
Lilia Brinza ◽  
...  

Author(s):  
Arthur M Lesk ◽  
Arun S Konagurthu

Abstract Motivation The gene expression regulatory network in yeast controls the selective implementation of the information contained in the genome sequence. We seek to understand how, in different physiological states, the network reconfigures itself to produce a different proteome. Results This article analyses this reconfiguration, focussing on changes in the local structure of the network. In particular, we define, extract and compare the 1-neighbourhoods of each transcription factor, where a 1-neighbourhood of a node in a network is the minimal subgraph of the network containing all nodes connected to the central node by an edge. We report the similarities and differences in the topologies and connectivities of these neighbourhoods in five physiological states for which data are available: cell cycle, DNA damage, stress response, diauxic shift and sporulation. Based on our analysis, it seems apt to regard the components of the regulatory network as ‘software’, and the responses to changes in state, ‘reprogramming’.


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