A cell cycle-coordinated nuclear compartment for Polymerase II transcription encompasses the earliest gene expression before global genome activation

2018 ◽  
Author(s):  
Idoia Quintana-Urzainqui
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Nuclear Compartment ◽  
A Cell ◽  
Genome Activation

scholarly journals A cell cycle-coordinated nuclear compartment for Polymerase II transcription encompasses the earliest gene expression before global genome activation

2018 ◽  
Author(s):  
Yavor Hadzhiev ◽  
Haseeb K. Qureshi ◽  
Lucy Wheatley ◽  
Ledean Cooper ◽  
Aleksandra Jasiulewicz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Temporal Dynamics ◽  
Nuclear Compartment ◽  
Cell Cycles ◽  
Regulatory Architecture ◽  
4D Imaging ◽  
Zygotic Gene ◽  
A Cell ◽  
Spatio Temporal ◽  
Genome Activation

AbstractMost metazoan embryos commence development with rapid cleavages without zygotic gene expression and their genome activation is delayed until the mid-blastula transition (MBT). However, a set of genes escape global repression during the extremely fast cell cycles, which lack gap phases and their transcription is activated before the MBT. Here we describe the formation and the spatio-temporal dynamics of a distinct transcription compartment, which encompasses the earliest detectable transcription during the first wave of genome activation. Simultaneous 4D imaging of expression of pri-miR430 and zinc finger genes by a novel, native transcription imaging approach reveals a pair of shared transcription compartments regulated by homolog chromosome organisation. These nuclear compartments carry the majority of nascent RNAs and transcriptionally active Polymerase II, are depleted of compact chromatin and represent the main sites for detectable transcription before MBT. We demonstrate that transcription occurs in the S-phase of the cleavage cycles and that the gradual slowing of these cell cycles are permissive to transcription before global genome activation. We propose that the demonstrated transcription compartment is part of the regulatory architecture of nucleus organisation, and provides a transcriptionally competent, supporting environment to facilitate early escape from the general nuclear repression before global genome activation.

scholarly journals A cell cycle-coordinated Polymerase II transcription compartment encompasses gene expression before global genome activation

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Yavor Hadzhiev ◽  
Haseeb K. Qureshi ◽  
Lucy Wheatley ◽  
Ledean Cooper ◽  
Aleksandra Jasiulewicz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
A Cell ◽  
Genome Activation

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.

scholarly journals Conserved Promoter Motif Is Required for Cell Cycle Timing of dnaX Transcription inCaulobacter

2001 ◽  
Vol 183 (16) ◽  
pp. 4860-4865 ◽  
Author(s):  
Kenneth C. Keiler ◽  
Lucy Shapiro
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Caulobacter Crescentus ◽  
Transcriptional Networks ◽  
Cellular Processes ◽  
Genes Encoding ◽  
Constitutive Gene Expression ◽  
A Cell ◽  
Replication Factors

ABSTRACT Cells use highly regulated transcriptional networks to control temporally regulated events. In the bacterium Caulobacter crescentus, many cellular processes are temporally regulated with respect to the cell cycle, and the genes required for these processes are expressed immediately before the products are needed. Genes encoding factors required for DNA replication, includingdnaX, dnaA, dnaN,gyrB, and dnaK, are induced at the G1/S-phase transition. By analyzing mutations in thednaX promoter, we identified a motif between the −10 and −35 regions that is required for proper timing of gene expression. This motif, named RRF (for repression of replication factors), is conserved in the promoters of other coordinately induced replication factors. Because mutations in the RRF motif result in constitutive gene expression throughout the cell cycle, this sequence is likely to be the binding site for a cell cycle-regulated transcriptional repressor. Consistent with this hypothesis, Caulobacter extracts contain an activity that binds specifically to the RRF in vitro.

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