Epigenetic markers and their cross-talk

2010 ◽  
Vol 48 ◽  
pp. 45-61 ◽  
Author(s):  
Stefan Winter ◽  
Wolfgang Fischle
Keyword(s):  
Cell Fate ◽  
Cross Talk ◽  
Cell Cycle Progression ◽  
Specific Binding ◽  
Cell Fate Determination ◽  
Chromatin Modifications ◽  
Cycle Progression ◽  
Post Translational Modifications ◽  
Histone Modifying Enzymes ◽  
Temporal And Spatial

Post-translational modifications of histone proteins in conjunction with DNA methylation represent important events in the regulation of local and global genome functions. Advances in the study of these chromatin modifications established temporal and spatial co-localization of several distinct ‘marks’ on the same histone and/or the same nucleosome. Such complex modification patterns suggest the possibility of combinatorial effects. This idea was originally proposed to establish a code of histone modifications that regulates the interpretation of the genetic code of DNA. Indeed, interdependency of different modifications is now well documented in the literature. Our current understanding is that the function of a given histone modification is influenced by neighbouring or additional modifications. Such context sensitivity of the readout of a modification provides more flexible translation than would be possible if distinct modifications function as isolated units. The mechanistic principles for modification cross-talk can originate in the modulation of the activity of histone-modifying enzymes or may be due to selective recognition of these marks via modification of specific binding proteins. In the present chapter, we discuss fundamental biochemical principles of modification cross-talk and reflect on the interplay of chromatin marks in cellular signalling, cell-cycle progression and cell-fate determination.

Life after meiosis: patterning the angiosperm male gametophyte

2010 ◽  
Vol 38 (2) ◽  
pp. 577-582 ◽  
Author(s):  
Michael Borg ◽  
David Twell
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Cell Cycle Progression ◽  
Male Gametophyte ◽  
Cell Fate Determination ◽  
Double Fertilization ◽  
Cycle Progression ◽  
Fate Determination ◽  
Male Gametogenesis ◽  
The Impact

Pollen grains represent the highly reduced haploid male gametophyte generation in angiosperms. They play an essential role in plant fertility by generating and delivering twin sperm cells to the embryo sac to undergo double fertilization. The functional specialization of the male gametophyte and double fertilization are considered to be key innovations in the evolutionary success of angiosperms. The haploid nature of the male gametophyte and its highly tractable ontogeny makes it an attractive system to study many fundamental biological processes, such as cell fate determination, cell-cycle progression and gene regulation. The present mini-review encompasses key advances in our understanding of the molecular mechanisms controlling male gametophyte patterning in angiosperms. A brief overview of male gametophyte development is presented, followed by a discussion of the genes required at landmark events of male gametogenesis. The value of the male gametophyte as an experimental system to study the interplay between cell fate determination and cell-cycle progression is also discussed and exemplified with an emerging model outlining the regulatory networks that distinguish the fate of the male germline from its sister vegetative cell. We conclude with a perspective of the impact emerging data will have on future research strategies and how they will develop further our understanding of male gametogenesis and plant development.

scholarly journals Single cell transcriptomics and developmental trajectories of murine cranial neural crest cell fate determination and cell cycle progression

2021 ◽  
Author(s):  
Yu Ji ◽  
Shuwen Zhang ◽  
Kurt Reynolds ◽  
Ran Gu ◽  
Moira McMahon ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Neural Crest ◽  
Single Cell ◽  
Cell Fate ◽  
Cell Cycle Progression ◽  
Developmental Trajectories ◽  
Cell Fate Determination ◽  
Cycle Progression ◽  
Fate Determination ◽  
Neural Lineage

Cranial neural crest (NC) cells migrate long distances to populate the future craniofacial regions and give rise to various tissues, including facial cartilage, bones, connective tissues, and cranial nerves. However, the mechanism that drives the fate determination of cranial NC cells remains unclear. Using single-cell RNA sequencing combined genetic fate mapping, we reconstructed developmental trajectories of cranial NC cells, and traced their differentiation in mouse embryos. We identified four major cranial NC cell lineages at different status: pre-epithelial-mesenchymal transition, early migration, NC-derived mesenchymal cells, and neural lineage cells from embryonic days 9.5 to 12.5. During migration, the first cell fate determination separates cranial sensory ganglia, the second generates mesenchymal progenitors, and the third separates other neural lineage cells. We then focused on the early facial prominences that appear to be built by undifferentiated, fast-dividing NC cells that possess similar transcriptomic landscapes, which could be the drive for the facial developmental robustness. The post-migratory cranial NC cells exit the cell cycle around embryonic day 11.5 after facial shaping is completed and initiates further fate determination and differentiation processes. Our results demonstrate the transcriptomic landscapes during dynamic cell fate determination and cell cycle progression of cranial NC lineage cells and also suggest that the transcriptomic regulation of the balance between proliferation and differentiation of the post-migratory cranial NC cells can be a key for building up unique facial structures in vertebrates.

scholarly journals Actual time-series of single-cell transcriptomics reveals circadian clocks as key regulators of cell differentiation in Arabidopsis

2020 ◽  
Author(s):  
Kotaro Torii ◽  
Keisuke Inoue ◽  
Keita Bekki ◽  
Kazuya Haraguchi ◽  
Minoru Kubo ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Differentiation ◽  
Circadian Clock ◽  
Single Cell ◽  
Cell Fate ◽  
Cell Cycle Progression ◽  
Circadian Clocks ◽  
Cell Fate Determination ◽  
Cycle Progression ◽  
Actual Time

Abstract The basis of toti/pluripotency is elaborate regulation of cell-cycle progression and cell-fate determination. Circadian clocks are involved in this process, but the underlying mechanisms have not been studied due to technical limitations. In particular, there is a lack of research on the universality of cell differentiation mechanisms in multicellular organisms using plants with high cell-fate plasticity. Here, exploiting in vivo single-cell RNA sequencing and a new actual time reconstitution method, PeakMacth, we analyzed actual time-series of cell reprogramming and differentiation processes at single-cell resolution, and found that the circadian clock modulates cell differentiation via BES1-mediated GSK3 signaling, which has a β-catenin-like function in Arabidopsis. In this pathway, the clock gene LUX in meristematic stem cells directly targets the CYCD and RETINOBLASTOMA-RELATED (RBR) genes, which are commonly involved in cell-cycle progression and cell-fate determination in plants and animals. In addition, the rhythmicity of the circadian clock was associated with cell state, and the establishment of the circadian rhythm preceded cell differentiation. Thus, our study not only reveals the involvement of the circadian clock in the differentiation of plant stem cells but also demonstrates functionally analogous features in the regulatory system of cell differentiation across species.

scholarly journals Phosphorylation of RCC1 on Serine 11 Facilitates G1/S Transition in HPV E7-Expressing Cells

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 995
Author(s):  
Xiaoyan Hou ◽  
Lijun Qiao ◽  
Ruijuan Liu ◽  
Xuechao Han ◽  
Weifang Zhang
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Cycle Regulation ◽  
Cell Cycle Progression ◽  
Mtor Pathway ◽  
Cycle Progression ◽  
Post Translational Modifications ◽  
Hpv E7 ◽  
Cycle Regulation

Persistent infection of high-risk human papillomavirus (HR-HPV) plays a causal role in cervical cancer. Regulator of chromosome condensation 1 (RCC1) is a critical cell cycle regulator, which undergoes a few post-translational modifications including phosphorylation. Here, we showed that serine 11 (S11) of RCC1 was phosphorylated in HPV E7-expressing cells. However, S11 phosphorylation was not up-regulated by CDK1 in E7-expressing cells; instead, the PI3K/AKT/mTOR pathway promoted S11 phosphorylation. Knockdown of AKT or inhibition of the PI3K/AKT/mTOR pathway down-regulated phosphorylation of RCC1 S11. Furthermore, S11 phosphorylation occurred throughout the cell cycle, and reached its peak during the mitosis phase. Our previous data proved that RCC1 was necessary for the G1/S cell cycle progression, and in the present study we showed that the RCC1 mutant, in which S11 was mutated to alanine (S11A) to mimic non-phosphorylation status, lost the ability to facilitate G1/S transition in E7-expressing cells. Moreover, RCC1 S11 was phosphorylated by the PI3K/AKT/mTOR pathway in HPV-positive cervical cancer SiHa and HeLa cells. We conclude that S11 of RCC1 is phosphorylated by the PI3K/AKT/mTOR pathway and phosphorylation of RCC1 S11 facilitates the abrogation of G1 checkpoint in HPV E7-expressing cells. In short, our study explores a new role of RCC1 S11 phosphorylation in cell cycle regulation.

scholarly journals The Saccharomyces cerevisiae Anaphase-Promoting Complex Interacts with Multiple Histone-Modifying Enzymes To Regulate Cell Cycle Progression

2010 ◽  
Vol 9 (10) ◽  
pp. 1418-1431 ◽  
Author(s):  
Emma L. Turner ◽  
Mackenzie E. Malo ◽  
Marnie G. Pisclevich ◽  
Megan D. Dash ◽  
Gerald F. Davies ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Chromatin Assembly ◽  
Temperature Sensitive ◽  
Anaphase Promoting Complex ◽  
Cycle Progression ◽  
Ubiquitin Ligase Complex ◽  
Genes Encoding ◽  
Dependent Cell ◽  
Histone Modifying Enzymes

ABSTRACT The anaphase-promoting complex (APC), a large evolutionarily conserved ubiquitin ligase complex, regulates cell cycle progression through mitosis and G1. Here, we present data suggesting that APC-dependent cell cycle progression relies on a specific set of posttranslational histone-modifying enzymes. Multiple APC subunit mutants were impaired in total and modified histone H3 protein content. Acetylated H3K56 (H3K56Ac) levels were as reduced as those of total H3, indicating that loading histones with H3K56Ac is unaffected in APC mutants. However, under restrictive conditions, H3K9Ac and dimethylated H3K79 (H3K79me2) levels were more greatly reduced than those of total H3. In a screen for histone acetyltransferase (HAT) and histone deacetylase (HDAC) mutants that genetically interact with the apc5 CA (chromatin assembly) mutant, we found that deletion of GCN5 or ELP3 severely hampered apc5 CA temperature-sensitive (ts) growth. Further analyses showed that (i) the elp3Δ gcn5Δ double mutant ts defect was epistatic to that observed in apc5 CA cells; (ii) gcn5Δ and elp3Δ mutants accumulate in mitosis; and (iii) turnover of the APC substrate Clb2 is not impaired in elp3Δ gcn5Δ cells. Increased expression of ELP3 and GCN5, as well as genes encoding the HAT Rtt109 and the chromatin assembly factors Msi1 and Asf1, suppressed apc5 CA defects, while increased APC5 expression partially suppressed elp3Δ gcn5Δ growth defects. Finally, we demonstrate that Gcn5 is unstable during G1 and following G1 arrest and is stabilized in APC mutants. We present our working model in which Elp3/Gcn5 and the APC work together to facilitate passage through mitosis and G1. To progress into S, we propose that at least Gcn5 must then be targeted for degradation in an APC-dependent fashion.

scholarly journals Cyclin E and CDK-2 regulate proliferative cell fate and cell cycle progression in the C. elegans germline

Development ◽  
2011 ◽  
Vol 138 (11) ◽  
pp. 2223-2234 ◽  
Author(s):  
P. M. Fox ◽  
V. E. Vought ◽  
M. Hanazawa ◽  
M.-H. Lee ◽  
E. M. Maine ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Cell Cycle Progression ◽  
Cyclin E ◽  
Cycle Progression ◽  
C Elegans ◽  
Proliferative Cell

scholarly journals Cellular responses to a prolonged delay in mitosis are determined by a DNA damage response controlled by Bcl-2 family proteins

Open Biology ◽  
2015 ◽  
Vol 5 (3) ◽  
pp. 140156 ◽  
Author(s):  
Didier J. Colin ◽  
Karolina O. Hain ◽  
Lindsey A. Allan ◽  
Paul R. Clarke
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Protein Kinases ◽  
Cell Fate ◽  
Dna Damage Response ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Anti Cancer ◽  
Damage Response ◽  
Microtubule Poisons

Anti-cancer drugs that disrupt mitosis inhibit cell proliferation and induce apoptosis, although the mechanisms of these responses are poorly understood. Here, we characterize a mitotic stress response that determines cell fate in response to microtubule poisons. We show that mitotic arrest induced by these drugs produces a temporally controlled DNA damage response (DDR) characterized by the caspase-dependent formation of γH2AX foci in non-apoptotic cells. Following exit from a delayed mitosis, this initial response results in activation of DDR protein kinases, phosphorylation of the tumour suppressor p53 and a delay in subsequent cell cycle progression. We show that this response is controlled by Mcl-1, a regulator of caspase activation that becomes degraded during mitotic arrest. Chemical inhibition of Mcl-1 and the related proteins Bcl-2 and Bcl-x L by a BH3 mimetic enhances the mitotic DDR, promotes p53 activation and inhibits subsequent cell cycle progression. We also show that inhibitors of DDR protein kinases as well as BH3 mimetics promote apoptosis synergistically with taxol (paclitaxel) in a variety of cancer cell lines. Our work demonstrates the role of mitotic DNA damage responses in determining cell fate in response to microtubule poisons and BH3 mimetics, providing a rationale for anti-cancer combination chemotherapies.

Epigenetic dynamics across the cell cycle

2010 ◽  
Vol 48 ◽  
pp. 107-120 ◽  
Author(s):  
Tony Bou Kheir ◽  
Anders H. Lund
Keyword(s):  
Cell Cycle ◽  
Chromosome Segregation ◽  
Cell Cycle Progression ◽  
Current Knowledge ◽  
Chromatin Condensation ◽  
Chromatin Modifications ◽  
Cycle Progression ◽  
Daughter Cells ◽  
Mammalian Cell Cycle ◽  
Regulate Cell Cycle Progression

Progression of the mammalian cell cycle depends on correct timing and co-ordination of a series of events, which are managed by the cellular transcriptional machinery and epigenetic mechanisms governing genome accessibility. Epigenetic chromatin modifications are dynamic across the cell cycle, and are shown to influence and be influenced by cell-cycle progression. Chromatin modifiers regulate cell-cycle progression locally by controlling the expression of individual genes and globally by controlling chromatin condensation and chromosome segregation. The cell cycle, on the other hand, ensures a correct inheritance of epigenetic chromatin modifications to daughter cells. In this chapter, we summarize the current knowledge on the dynamics of epigenetic chromatin modifications during progression of the cell cycle.

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