scholarly journals Emergence of the subapical domain is associated with the midblastula transition

2019 ◽  
Author(s):  
Anja Schmidt ◽  
Jörg Großhans
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
De Novo ◽  
Strong Increase ◽  
Cell Cortex ◽  
Midblastula Transition ◽  
Zygotic Transcription ◽  
Zygotic Gene ◽  
Cortical Patterning ◽  
A Cell

AbstractEpithelial domains and cell polarity are determined by polarity proteins which are associated with the cell cortex in a spatially restricted pattern. Early Drosophila embryos are characterized by a stereotypic dynamic and de novo formation of cortical domains. For example, the subapical domain emerges at the transition from syncytial to cellular development during the first few minutes of interphase 14. The dynamics in cortical patterning is revealed by the subapical markers Canoe/Afadin and ELMO-Sponge, which widely distributed in interphase 13 but subapically restricted in interphase 14. The factors and mechanism determining the timing for the emergence of the subapical domain have been unknown. In this study, we show, that the restricted localization of subapical markers depends on the onset of zygotic gene expression. In contrast to cell cycle remodeling, the emergence of the subapical domain does not depend on the nucleo-cytoplasmic ratio. Thus, we define cortical dynamics and specifically the emergence of the subapical domain as a feature of the midblastula transition.Author summaryMidblastula transition is a paradigm of a developmental transition. Multiple processes such as cell cycle, cell mobility, onset of zygotic gene expression, degradation of maternal RNA and chromatin structure are coordinated to lead to defined changes in visible morphology. The midblastula transition in Drosophila embryos is associated with a change from fast nuclear cycles to a cell cycle mode with gap phase and slow replication, a strong increase in zygotic transcription and cellularization. The timing of the processes associated with the midblastula transition are controlled by the onset of zygotic gene expression or the nucleocytoplasmic ratio. Here we define the patterning of cortical domains, i. e. the emergence of a subapical domain as a novel feature of the midblastula transition whose appearance is controlled by the onset of zygotic transcription but not the nucleocytoplasmic ratio. Our findings will help to gain further understanding of the coordination of complex developmental processes during the midblastula transition.

scholarly journals Human Immunodeficiency Virus Type 1 (HIV-1) Vpr Functions as an Immediate-Early Protein during HIV-1 Infection

1999 ◽  
Vol 73 (5) ◽  
pp. 4101-4109 ◽  
Author(s):  
Mohammed Hrimech ◽  
Xiao-Jian Yao ◽  
François Bachand ◽  
Nicole Rougeau ◽  
Éric A. Cohen
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Human Immunodeficiency Virus ◽  
De Novo ◽  
Proliferating Cells ◽  
Early Protein ◽  
Immunodeficiency Virus ◽  
A Cell ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) Vpr is a virion-associated protein which facilitates HIV-1 infection of nondividing cells by contributing to the nuclear transport of the preintegration complex (PIC). Vpr was also shown to induce a cell cycle G2 arrest in infected proliferating cells that optimizes HIV-1 long terminal repeat (LTR)-directed gene expression and viral production. However, it is unclear whether this activity is mediated primarily early by virion-associated Vpr or alternatively late during infection when Vpr is de novo expressed. We report here that in the absence of de novo expression, virion-associated Vpr induces a transient G2 arrest that can subsequently lead to cell killing by apoptosis. Interestingly, the induction of both cell cycle G2 arrest and apoptosis by virion-associated Vpr requires viral entry but not viral replication, since reverse transcriptase and protease inhibitor treatments do not prevent these Vpr effects. These results raise the possibility that in vivo both infectious and noninfectious viruses contribute to the dysfunction and killing of CD4+ cells. In addition, our results reveal that virion-associated Vpr stimulates viral replication in proliferating cells after establishing a cell cycle G2 arrest by increasing LTR-directed gene expression. Importantly, this Vpr-mediated LTR activation appears to be a requirement for subsequent optimal Tat transactivation. Taken together, these results strongly suggest that in addition to participating in the HIV PIC nuclear transport in nondividing cells, virion-associated Vpr activates HIV-1 LTR-directed gene expression by manipulating the host cell cycle. From this, we conclude that Vpr functions as an immediate-early protein during HIV-1 infection.

scholarly journals Effects of cell cycle variability on lineage and population measurements of mRNA abundance

2020 ◽  
Author(s):  
Ruben Perez-Carrasco ◽  
Casper Beentjes ◽  
Ramon Grima
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Negative Binomial ◽  
Eukaryotic Cell ◽  
Cycle Duration ◽  
Cell Cycle Duration ◽  
Monotonically Decreasing Function ◽  
Binomial Mixture ◽  
A Cell ◽  
The Mean

AbstractMany models of gene expression do not explicitly incorporate a cell cycle description. Here we derive a theory describing how mRNA fluctuations for constitutive and bursty gene expression are influenced by stochasticity in the duration of the cell cycle and the timing of DNA replication. Analytical expressions for the moments show that omitting cell cycle duration introduces an error in the predicted mean number of mRNAs that is a monotonically decreasing function of η, which is proportional to the ratio of the mean cell cycle duration and the mRNA lifetime. By contrast, the error in the variance of the mRNA distribution is highest for intermediate values of η consistent with genome-wide measurements in many organisms. Using eukaryotic cell data, we estimate the errors in the mean and variance to be at most 3% and 25%, respectively. Furthermore, we derive an accurate negative binomial mixture approximation to the mRNA distribution. This indicates that stochasticity in the cell cycle can introduce fluctuations in mRNA numbers that are similar to the effect of bursty transcription. Finally, we show that for real experimental data, disregarding cell cycle stochasticity can introduce errors in the inference of transcription rates larger than 10%.

scholarly journals Repurposing of KLF5 activates a cell cycle signature during the progression from a precursor state to oesophageal adenocarcinoma

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Connor Rogerson ◽  
Samuel Ogden ◽  
Edward Britton ◽  
Yeng Ang ◽  
Andrew D Sharrocks ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Prognostic Significance ◽  
Gene Expression Signature ◽  
Chromatin Accessibility ◽  
Oesophageal Adenocarcinoma ◽  
Cell Cycle Gene ◽  
Molecular Events ◽  
Common Causes ◽  
A Cell

Oesophageal adenocarcinoma (OAC) is one of the most common causes of cancer deaths. Barrett’s oesophagus (BO) is the only known precancerous precursor to OAC, but our understanding about the molecular events leading to OAC development is limited. Here, we have integrated gene expression and chromatin accessibility profiles of human biopsies and identified a strong cell cycle gene expression signature in OAC compared to BO. Through analysing associated chromatin accessibility changes, we have implicated the transcription factor KLF5 in the transition from BO to OAC. Importantly, we show that KLF5 expression is unchanged during this transition, but instead, KLF5 is redistributed across chromatin to directly regulate cell cycle genes specifically in OAC cells. This new KLF5 target gene programme has potential prognostic significance as high levels correlate with poorer patient survival. Thus, the repurposing of KLF5 for novel regulatory activity in OAC provides new insights into the mechanisms behind disease progression.

scholarly journals Repurposing of KLF5 activates a cell cycle signature during the progression from a precursor state to Oesophageal Adenocarcinoma

2020 ◽  
Author(s):  
Connor Rogerson ◽  
Samuel Ogden ◽  
Edward Britton ◽  
Yeng Ang ◽  
Andrew D. Sharrocks ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Prognostic Significance ◽  
Gene Expression Signature ◽  
Chromatin Accessibility ◽  
Oesophageal Adenocarcinoma ◽  
Cell Cycle Gene ◽  
A Cell

AbstractOesophageal adenocarcinoma (OAC) is one of the most common causes of cancer deaths and yet compared to other common cancers, we know relatively little about the underlying molecular mechanisms. Barrett’s oesophagus (BO) is the only known precancerous precursor to OAC, but our understanding about the specific events leading to OAC development is limited. Here, we have integrated gene expression and chromatin accessibility profiles of human biopsies of BO and OAC and identified a strong cell cycle gene expression signature in OAC compared to BO. Through analysing associated chromatin accessibility changes, we have implicated the transcription factor KLF5 in the transition from BO to OAC. Importantly, we show that KLF5 expression is unchanged during this transition, but instead, KLF5 is redistributed across chromatin in OAC cells to directly regulate cell cycle genes specifically in OAC. Our findings have potential prognostic significance as the survival of patients with high expression of KLF5 target genes is significantly lower. We have provided new insights into the gene expression networks in OAC and the mechanisms behind progression to OAC, chiefly the repurposing of KLF5 for novel regulatory activity in OAC.

scholarly journals The Gene Expression and Enzyme Activity of Plant 3-Deoxy-D-Manno-2-Octulosonic Acid-8-Phosphate Synthase Are Preferentially Associated with Cell Division in a Cell Cycle-Dependent Manner

2003 ◽  
Vol 133 (1) ◽  
pp. 348-360 ◽  
Author(s):  
Frédéric Delmas ◽  
Johann Petit ◽  
Jérôme Joubès ◽  
Martial Séveno ◽  
Thomas Paccalet ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Enzyme Activity ◽  
Cell Division ◽  
Dependent Manner ◽  
A Cell ◽  
Cycle Dependent ◽  
Phosphate Synthase

scholarly journals Investigating the Central Dogma of Molecular Biology in the Context of Nuclear Architecture and Cell Cycle

2019 ◽  
Author(s):  
Shivnarayan Dhuppar ◽  
Aprotim Mazumder
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Single Molecule ◽  
Mammalian Cells ◽  
Nuclear Architecture ◽  
Nuclear Lamina ◽  
Gene Copy ◽  
A Cell ◽  
Cycle Dependent

AbstractNuclear architecture is the organization of the genome within a cell nucleus with respect to different nuclear landmarks such as nuclear lamina, matrix or nucleoli. Lately it has emerged as a major regulator of gene expression in mammalian cells. The studies connecting nuclear architecture with gene expression are largely population-averaged and do not report on the heterogeneity in genome organization or in gene expression within a population. In this report we present a method for combining 3D DNA Fluorescence in situ Hybridization (FISH) with single molecule RNA FISH (smFISH) and immunofluorescence to study nuclear architecture-dependent gene regulation on a cell-by-cell basis. We further combine it with an imaging-based cell cycle staging to correlate nuclear architecture with gene expression across the cell cycle. We present this in the context of Cyclin A2 (CCNA2) gene for its known cell cycle-dependent expression. We show that, across the cell cycle, the expression of a CCNA2 gene copy is stochastic and depends neither on its sub-nuclear position—which usually lies close to nuclear lamina—nor on the expression from the other copies.

Identification of a Cell Cycle-Dependent Duplicating Complex that Assembles Basal Bodies de novo in Naegleria

Protist ◽  
2015 ◽  
Vol 166 (1) ◽  
pp. 1-13 ◽  
Author(s):  
JungHa Lee ◽  
Seungmin Kang ◽  
Yong Seok Choi ◽  
Hong-Kyung Kim ◽  
Chang-Yeol Yeo ◽  
...  
Keyword(s):  
Cell Cycle ◽  
De Novo ◽  
Basal Bodies ◽  
A Cell ◽  
Cycle Dependent

scholarly journals Histone supply regulates S phase timing and cell cycle progression

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Ufuk Günesdogan ◽  
Herbert Jäckle ◽  
Alf Herzig
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
De Novo ◽  
S Phase ◽  
Histone Genes ◽  
Nucleosome Assembly ◽  
Cycle Progression ◽  
Cycle Arrest ◽  
A Cell ◽  
Surveillance Mechanism

Eukaryotes package DNA into nucleosomes that contain a core of histone proteins. During DNA replication, nucleosomes are disrupted and re-assembled with newly synthesized histones and DNA. Despite much progress, it is still unclear why higher eukaryotes contain multiple core histone genes, how chromatin assembly is controlled, and how these processes are coordinated with cell cycle progression. We used a histone null mutation of Drosophila melanogaster to show that histone supply levels, provided by a defined number of transgenic histone genes, regulate the length of S phase during the cell cycle. Lack of de novo histone supply not only extends S phase, but also causes a cell cycle arrest during G2 phase, and thus prevents cells from entering mitosis. Our results suggest a novel cell cycle surveillance mechanism that monitors nucleosome assembly without involving the DNA repair pathways and exerts its effect via suppression of CDC25 phosphatase String expression.

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