scholarly journals Crystallin gene expression: Insights from studies of transcriptional bursting

2021 ◽  
Vol 207 ◽  
pp. 108564
Author(s):  
Ales Cvekl ◽  
Carolina Eliscovich
Keyword(s):  
Gene Expression ◽  
Transcriptional Bursting

scholarly journals Properties of Gene Expression and Chromatin Structure with Mechanically Regulated Transcription

2018 ◽  
Author(s):  
Stuart A. Sevier ◽  
Herbert Levine
Keyword(s):  
Gene Expression ◽  
Mechanical Properties ◽  
Dna Structure ◽  
Genetic System ◽  
Dna Supercoiling ◽  
Simple Description ◽  
Gene Orientation ◽  
Physical Elements ◽  
Transcriptional Bursting ◽  
The Impact

The mechanical properties of transcription have emerged as central elements in our understanding of gene expression. Recent work has been done introducing a simple description of the basic physical elements of transcription where RNA elongation, RNA polymerase (RNAP) rotation and DNA supercoiling are coupled [1]. Here we generalize this framework to accommodate the behavior of many RNAPs operating on multiple genes on a shared piece of DNA. The resulting framework is combined with well-established stochastic processes of transcription resulting in a model which characterizes the impact of the mechanical properties of transcription on gene expression and DNA structure. Transcriptional bursting readily emerges as a common phenomenon with origins in the geometric nature of the genetic system and results in the bounding of gene expression statistics. Properties of a multiple gene system are examined with special attention paid to role that genome composition (gene orientation, size, and intergenic distance) plays in the ability of genes to transcribe. The role of transcription in shaping DNA structure is examined and the possibility of transcription driven domain formation is discussed.PACS numbers:

scholarly journals TriTag: an integrative tool to correlate chromatin dynamics and gene expression in living cells

2020 ◽  
Vol 48 (22) ◽  
pp. e127-e127 ◽  
Author(s):  
Haiyue Xu ◽  
Junyan Wang ◽  
Ying Liang ◽  
Yujuan Fu ◽  
Sihui Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Fluorescent Protein ◽  
Chromatin Dynamics ◽  
Endogenous Gene ◽  
Dna Labeling ◽  
Functional Capabilities ◽  
Protein Tracking ◽  
Response To Stress ◽  
Transcriptional Bursting

Abstract A wealth of single-cell imaging studies have contributed novel insights into chromatin organization and gene regulation. However, a comprehensive understanding of spatiotemporal gene regulation requires developing tools to combine multiple monitoring systems in a single study. Here, we report a versatile tag, termed TriTag, which integrates the functional capabilities of CRISPR-Tag (DNA labeling), MS2 aptamer (RNA imaging) and fluorescent protein (protein tracking). Using this tag, we correlate changes in chromatin dynamics with the progression of endogenous gene expression, by recording both transcriptional bursting and protein production. This strategy allows precise measurements of gene expression at single-allele resolution across the cell cycle or in response to stress. TriTag enables capturing an integrated picture of gene expression, thus providing a powerful tool to study transcriptional heterogeneity and regulation.

scholarly journals On-microscope staging of live cells reveals changes in the dynamics of transcriptional bursting during differentiation

2021 ◽  
Author(s):  
Danuta M Jeziorska ◽  
Edward A J Tunnacliffe ◽  
Jill M Brown ◽  
Helena Ayyub ◽  
Jacqueline A Sloane-Stanley ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mammalian Cells ◽  
Transcriptional Activity ◽  
Dynamic Behaviour ◽  
Live Cells ◽  
Development And Differentiation ◽  
The Stability ◽  
Transcriptional Bursting ◽  
Behaviour Changes ◽  
Transcriptional State

Determining the mechanisms by which genes are switched on and off during development and differentiation is a key aim of current biomedical research. Gene transcription has been widely observed to occur in a discontinuous fashion, with short bursts of activity interspersed with longer periods of inactivity. It is currently not known if or how this dynamic behaviour changes as mammalian cells differentiate. To investigate this, using a newly developed on-microscope analysis, we monitored mouse α-globin transcription in live cells throughout sequential stages of erythropoiesis. We find that changes in the overall levels of α-globin transcription are most closely associated with changes in the fraction of time a gene spends in the active transcriptional state. We identify differences in the patterns of transcriptional bursting throughout differentiation, with maximal transcriptional activity occurring in the mid-phase of differentiation. Early in differentiation, we observe increased fluctuation in the patterns of transcriptional activity whereas at the peak of gene expression, in early and intermediate erythroblasts, transcription appears to be relatively stable and efficient. Later during differentiation as α-globin expression declines, we again observed more variability in transcription within individual cells. We propose that the observed changes in transcriptional behaviour may reflect changes in the stability of enhancer-promoter interactions and the formation of active transcriptional compartments as gene expression is turned on and subsequently declines at sequential stages of differentiation.

scholarly journals Transcriptional Bursting from the HIV-1 Promoter Is a Significant Source of Stochastic Noise in HIV-1 Gene Expression

2010 ◽  
Vol 98 (8) ◽  
pp. L32-L34 ◽  
Author(s):  
Abhyudai Singh ◽  
Brandon Razooky ◽  
Chris D. Cox ◽  
Michael L. Simpson ◽  
Leor S. Weinberger
Keyword(s):  
Gene Expression ◽  
Significant Source ◽  
Stochastic Noise ◽  
Transcriptional Bursting ◽  
Hiv 1

scholarly journals Mammalian gene expression variability is explained by underlying cell state

2019 ◽  
Author(s):  
Robert Foreman ◽  
Roy Wollman
Keyword(s):  
Gene Expression ◽  
Mammalian Cells ◽  
Qualitative Difference ◽  
Live Cells ◽  
Expression Variability ◽  
Cell State ◽  
Relative Contribution ◽  
Allele Specific ◽  
Poisson Limit ◽  
Transcriptional Bursting

AbstractGene expression variability in mammalian systems plays an important role in physiological and pathophysiological conditions. This variability can come from differential regulation related to cell state (extrinsic) and allele-specific transcriptional bursting (intrinsic). Yet, the relative contribution of these two distinct sources is unknown. Here we exploit the qualitative difference in the patterns of covariance between these two sources to quantify their relative contributions to expression variance in mammalian cells. Using multiplexed error robust RNA fluorescent in situ hybridization (MERFISH) we measured the multivariate gene expression distribution of 150 genes related to Ca2+ signaling coupled with the dynamic Ca2+ response of live cells to ATP. We show that after controlling for cellular phenotypic states such as size, cell cycle stage, and Ca2+ response to ATP, the remaining variability is effectively at the Poisson limit for most genes. These findings demonstrate that the majority of expression variability results from cell state differences and that the contribution of transcriptional bursting is relatively minimal.

scholarly journals Stochastic steady state gain in a gene expression process with mRNA degradation control

2012 ◽  
Vol 9 (72) ◽  
pp. 1589-1598 ◽  
Author(s):  
Hiroyuki Kuwahara ◽  
Russell Schwartz
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Steady State ◽  
Protein Level ◽  
Mrna Level ◽  
System Level ◽  
Wide Range ◽  
Molecular Reactions ◽  
Transcriptional Bursting ◽  
Regulation Model

Recent analyses with high-resolution single-molecule experimental methods have shown highly irregular and variable bursting of mRNA in a wide range of organisms. Noise in gene expression is thought to be beneficial in cell fate specifications, as it can lay a foundation for phenotypic diversification of isogenetic cells in the homogeneous environment. However, because the stability of proteins is, in many cases, higher than that of mRNAs, noise from transcriptional bursting can be considerably buffered at the protein level, limiting the effect of noisy mRNAs at a more global regulation level. This raises a question as to what constructive role noisy mRNAs can play in the system-level dynamics. In this study, we have addressed this question using the computational models that extend the conventional transcriptional bursting model with a post-transcriptional regulation step. Surprisingly, by comparing this stochastic model with the corresponding deterministic model, we find that intrinsic fluctuations can substantially increase the expected mRNA level. Because effects of a higher mRNA level can be transmitted to the protein level even with slow protein degradation rates, this finding suggests that an increase in the protein level is another potential effect of transcriptional bursting. Here, we show that this striking steady state increase is caused by the asynchronous nature of molecular reactions, which allows the transcriptional regulation model to create additional modes of qualitatively distinct dynamics. Our results illustrate non-intuitive effects of reaction asynchronicity on system dynamics that cannot be captured by the traditional deterministic framework. Because molecular reactions are intrinsically stochastic and asynchronous, these findings may have broad implications in modelling and understanding complex biological systems.

scholarly journals Mechanical bounds to transcriptional noise

2016 ◽  
Vol 113 (49) ◽  
pp. 13983-13988 ◽  
Author(s):  
Stuart A. Sevier ◽  
David A. Kessler ◽  
Herbert Levine
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Phenomenological Model ◽  
Copy Number ◽  
Probability Distributions ◽  
Intrinsic Noise ◽  
Universal Curve ◽  
Stochastic Effects ◽  
The Past ◽  
Transcriptional Bursting

Over the past several decades it has been increasingly recognized that stochastic processes play a central role in transcription. Although many stochastic effects have been explained, the source of transcriptional bursting (one of the most well-known sources of stochasticity) has continued to evade understanding. Recent results have pointed to mechanical feedback as the source of transcriptional bursting, but a reconciliation of this perspective with preexisting views of transcriptional regulation is lacking. In this article, we present a simple phenomenological model that is able to incorporate the traditional view of gene expression within a framework with mechanical limits to transcription. By introducing a simple competition between mechanical arrest and relaxation copy number probability distributions collapse onto a shared universal curve under shifting and rescaling and a lower limit of intrinsic noise for any mean expression level is found.

scholarly journals Dynamic regulation of anterior-posterior patterning genes in living Drosophila embryos

2020 ◽  
Author(s):  
Takashi Fukaya
Keyword(s):  
Gene Expression ◽  
Transcriptional Activation ◽  
Anterior Part ◽  
Expression Patterns ◽  
Total Duration ◽  
Total Output ◽  
Expression Domain ◽  
Stripe Pattern ◽  
Transcriptional Bursting ◽  
Pair Rule

SummaryExpression of the gap and pair-rule genes plays an essential role in body segmentation during Drosophila embryogenesis [1–5]. However, it remains unclear how precise expression patterns of these key developmental genes arise from stochastic transcriptional activation at the single cell level. Here, I employed genome editing and live imaging approaches to comprehensively visualize regulation of the gap and pair-rule genes at the endogenous loci. Quantitative image analysis revealed that the total duration of active transcription (transcription period) is a major determinant of spatial patterning of gene expression in early embryos. The length of transcription period is regulated by the continuity of bursting activities in individual nuclei, with core expression domain producing more bursts than boundary region. Each gene exhibits distinct rate of nascent RNA production during transcriptional bursting, which contributes to gene-to-gene variability in the total output. I also provide evidence for “enhancer competition”, wherein a distal weak enhancer interferes with transcriptional activation by a strong proximal enhancer to downregulate the length of transcription period without changing the transcription rate. Analysis of endogenous hunchback (hb) locus revealed that the removal of distal shadow enhancer induces strong ectopic transcriptional activation, which suppresses refinement of broad expression domain into narrower stripe pattern at the anterior part of embryos. This study provides key insights into the link between transcriptional bursting, enhancer-promoter interaction and spatiotemporal patterning of gene expression during animal development.

scholarly journals Genome-wide kinetic properties of transcriptional bursting in mouse embryonic stem cells

2020 ◽  
Vol 6 (25) ◽  
pp. eaaz6699 ◽  
Author(s):  
Hiroshi Ochiai ◽  
Tetsutaro Hayashi ◽  
Mana Umeda ◽  
Mika Yoshimura ◽  
Akihito Harada ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Mammalian Cells ◽  
Transcription Elongation ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Kinetic Properties ◽  
Mrna Levels ◽  
Transcriptional Bursting

Transcriptional bursting is the stochastic activation and inactivation of promoters, contributing to cell-to-cell heterogeneity in gene expression. However, the mechanism underlying the regulation of transcriptional bursting kinetics (burst size and frequency) in mammalian cells remains elusive. In this study, we performed single-cell RNA sequencing to analyze the intrinsic noise and mRNA levels for elucidating the transcriptional bursting kinetics in mouse embryonic stem cells. Informatics analyses and functional assays revealed that transcriptional bursting kinetics was regulated by a combination of promoter- and gene body–binding proteins, including the polycomb repressive complex 2 and transcription elongation factors. Furthermore, large-scale CRISPR-Cas9–based screening identified that the Akt/MAPK signaling pathway regulated bursting kinetics by modulating transcription elongation efficiency. These results uncovered the key molecular mechanisms underlying transcriptional bursting and cell-to-cell gene expression noise in mammalian cells.

scholarly journals Flipping between Polycomb repressed and active transcriptional states introduces noise in gene expression

2017 ◽  
Author(s):  
Gozde Kar ◽  
Jong Kyoung Kim ◽  
Aleksandra A. Kolodziejczyk ◽  
Kedar Nath Natarajan ◽  
Elena Torlai Triglia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Polymerase Ii ◽  
Burst Size ◽  
Three Dimensions ◽  
Sequencing Data ◽  
Gene Expression Noise ◽  
Histone Modifiers ◽  
Transcriptional Bursting ◽  
Noise In Gene Expression ◽  
Active Genes

AbstractPolycomb repressive complexes (PRCs) are important histone modifiers, which silence gene expression, yet there exists a subset of PRC-bound genes actively transcribed by RNA polymerase II (RNAPII). It is likely that the role of PRC is to dampen expression of these PRC-active genes. However, it is unclear how this flipping between chromatin states alters the kinetics of transcriptional burst size and frequency relative to genes with exclusively activating marks. To investigate this, we integrate histone modifications and RNAPII states derived from bulk ChIP-seq data with single-cell RNA-sequencing data. We find that PRC-active genes have a greater cell-to-cell variation in expression than active genes with the same mean expression levels, and validate these results by knockout experiments. We also show that PRC-active genes are clustered on chromosomes in both two and three dimensions, and interactions with active enhancers promote a stabilization of gene expression noise. These findings provide new insights into how chromatin regulation modulates stochastic gene expression and transcriptional bursting, with implications for regulation of pluripotency and development.

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