scholarly journals A spatial stochastic model reveals the role of supercoiling in transcription regulation

2021 ◽  
Author(s):  
Yuncong Geng ◽  
Christopher Herrick Bohrer ◽  
Nicolás Yehya ◽  
Hunter Hendrix ◽  
Lior Shachaf ◽  
...  
Keyword(s):  
Transcription Regulation ◽  
Genome Organization ◽  
Experimental Investigations ◽  
Domain Formation ◽  
Transcription Regulator ◽  
Topological Domain ◽  
Spatially Resolved ◽  
Accessible Information ◽  
Highly Expressed Genes

In Escherichia coli, translocation of RNA polymerase (RNAP) during transcription introduces supercoiling to DNA, which influences the initiation and elongation behaviors of RNAP. To quantify the role of supercoiling in transcription regulation, we develop a spatially resolved supercoiling model of transcription, describing RNAP-supercoiling interactions, topoisomerase activities, stochastic topological domain formation, and supercoiling diffusion in all transcription stages. This model establishes that transcription-induced supercoiling mediates the cooperation of co-transcribing RNAP molecules in highly expressed genes. It reveals that supercoiling transmits RNAP-accessible information through DNA and enables different RNAP molecules to communicate within and between genes. It thus predicts that a topological domain could serve as a transcription regulator, generating substantial transcription bursting and coordinating communications between adjacent genes in the domain. The model provides a quantitative platform for further theoretical and experimental investigations of how genome organization impacts transcription.

scholarly journals Simultaneous epigenetic perturbation and genome imaging reveal distinct roles of H3K9me3 in chromatin architecture and transcription

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying Feng ◽  
Yao Wang ◽  
Xiangnan Wang ◽  
Xiaohui He ◽  
Chen Yang ◽  
...  
Keyword(s):  
Genome Organization ◽  
Transcriptional Repression ◽  
De Novo ◽  
Active Regions ◽  
Gene Repression ◽  
Domain Formation ◽  
Transcriptional Initiation ◽  
Chromatin Architecture ◽  
Small Set

Abstract Introduction Despite the long-observed correlation between H3K9me3, chromatin architecture, and transcriptional repression, how H3K9me3 regulates genome higher-order organization and transcriptional activity in living cells remains unclear. Result Here, we develop EpiGo (Epigenetic perturbation induced Genome organization)-KRAB to introduce H3K9me3 at hundreds of loci spanning megabases on human chromosome 19 and simultaneously track genome organization. EpiGo-KRAB is sufficient to induce genomic clustering and de novo heterochromatin-like domain formation, which requires SETDB1, a methyltransferase of H3K9me3. Unexpectedly, EpiGo-KRAB-induced heterochromatin-like domain does not result in widespread gene repression except a small set of genes with concurrent loss of H3K4me3 and H3K27ac. Ectopic H3K9me3 appears to spread in inactive regions but is largely restricted from transcriptional initiation sites in active regions. Finally, Hi-C analysis showed that EpiGo-KRAB reshapes existing compartments mainly at compartment boundaries. Conclusions These results reveal the role of H3K9me3 in genome organization could be partially separated from its function in gene repression.

scholarly journals Simultaneous Epigenetic Perturbation and Genome Imaging Reveal Distinct Roles of H3K9me3 in Chromatin Architecture and Transcription

2020 ◽  
Author(s):  
Ying Feng ◽  
Yao Wang ◽  
Xiangnan Wang ◽  
Xiaohui He ◽  
Chen Yang ◽  
...  
Keyword(s):  
Genome Organization ◽  
Transcriptional Repression ◽  
De Novo ◽  
Active Regions ◽  
Gene Repression ◽  
Domain Formation ◽  
Transcriptional Initiation ◽  
Chromatin Architecture ◽  
Small Set

AbstractDespite the long-observed correlation between H3K9me3, chromatin architecture and transcriptional repression, how H3K9me3 regulates genome higher-order organization and transcriptional activity in living cells remains unclear. Here we develop EpiGo (Epigenetic perturbation induced Genome organization)-KRAB to introduce H3K9me3 at hundreds of loci spanning megabases on human chromosome 19 and simultaneously track genome organization. EpiGo-KRAB is sufficient to induce de novo heterochromatin-like domain formation, which requires SETDB1, a methyltransferase of H3K9me3. Unexpectedly, EpiGo-KRAB induced heterochromatin-like domain does not result in widespread gene repression except a small set of genes with concurrent loss of H3K4me3 and H3K27ac. Ectopic H3K9me3 appears to spread in inactive regions but is largely restricted to transcriptional initiation sites in active regions. Finally, Hi-C analysis showed that EpiGo-KRAB induced to reshape existing compartments. These results reveal the role of H3K9me3 in genome organization could be partially separated from its function in gene repression.

scholarly journals Bringing high spatial resolution to the far-infrared

2021 ◽  
Author(s):  
Hendrik Linz ◽  
Henrik Beuther ◽  
Maryvonne Gerin ◽  
Javier R. Goicoechea ◽  
Frank Helmich ◽  
...  
Keyword(s):  
Spatial Resolution ◽  
Formation Process ◽  
Far Infrared ◽  
Main Theme ◽  
Spatially Resolved ◽  
Research Areas ◽  
External Galaxies ◽  
Emergence Of Life ◽  
Fine Structure Lines

AbstractThe far-infrared (FIR) regime is one of the wavelength ranges where no astronomical data with sub-arcsecond spatial resolution exist. None of the medium-term satellite projects like SPICA, Millimetron, or the Origins Space Telescope will resolve this malady. For many research areas, however, information at high spatial and spectral resolution in the FIR, taken from atomic fine-structure lines, from highly excited carbon monoxide (CO), light hydrides, and especially from water lines would open the door for transformative science. A main theme will be to trace the role of water in proto-planetary discs, to observationally advance our understanding of the planet formation process and, intimately related to that, the pathways to habitable planets and the emergence of life. Furthermore, key observations will zoom into the physics and chemistry of the star-formation process in our own Galaxy, as well as in external galaxies. The FIR provides unique tools to investigate in particular the energetics of heating, cooling, and shocks. The velocity-resolved data in these tracers will reveal the detailed dynamics engrained in these processes in a spatially resolved fashion, and will deliver the perfect synergy with ground-based molecular line data for the colder dense gas.

The role of Su(Hw) protein in transcription regulation in Drosophila melanogaster

2015 ◽  
Vol 51 (11) ◽  
pp. 1060-1068
Author(s):  
P. V. Elizar’ev ◽  
D. A. Chetverina ◽  
A. K. Golovnin ◽  
P. G. Georgiev ◽  
M. M. Erokhin
Keyword(s):  
Drosophila Melanogaster ◽  
Transcription Regulation

On velocity gradient dynamics and turbulent structure

2015 ◽  
Vol 780 ◽  
pp. 60-98 ◽  
Author(s):  
J. M. Lawson ◽  
J. R. Dawson
Keyword(s):  
Velocity Gradient ◽  
Local Strain ◽  
Turbulent Structure ◽  
Stochastic Estimation ◽  
Spatially Resolved ◽  
Gradient Dynamics ◽  
Layer Structures ◽  
Non Local ◽  
Conditional Averaging

The statistics of the velocity gradient tensor $\unicode[STIX]{x1D63C}=\boldsymbol{{\rm\nabla}}\boldsymbol{u}$, which embody the fine scales of turbulence, are influenced by turbulent ‘structure’. Whilst velocity gradient statistics and dynamics have been well characterised, the connection between structure and dynamics has largely focused on rotation-dominated flow and relied upon data from numerical simulation alone. Using numerical and spatially resolved experimental datasets of homogeneous turbulence, the role of structure is examined for all local (incompressible) flow topologies characterisable by $\unicode[STIX]{x1D63C}$. Structures are studied through the footprints they leave in conditional averages of the $Q=-\text{Tr}(\unicode[STIX]{x1D63C}^{2})/2$ field, pertinent to non-local strain production, obtained using two complementary conditional averaging techniques. The first, stochastic estimation, approximates the $Q$ field conditioned upon $\unicode[STIX]{x1D63C}$ and educes quantitatively similar structure in both datasets, dissimilar to that of random Gaussian velocity fields. Moreover, it strongly resembles a promising model for velocity gradient dynamics recently proposed by Wilczek & Meneveau (J. Fluid Mech., vol. 756, 2014, pp. 191–225), but is derived under a less restrictive premise, with explicitly determined closure coefficients. The second technique examines true conditional averages of the $Q$ field, which is used to validate the stochastic estimation and provide insights towards the model’s refinement. Jointly, these approaches confirm that vortex tubes are the predominant feature of rotation-dominated regions and additionally show that shear layer structures are active in strain-dominated regions. In both cases, kinematic features of these structures explain alignment statistics of the pressure Hessian eigenvectors and why local and non-local strain production act in opposition to each other.

scholarly journals The universally-conserved transcription factor RfaH is recruited to a hairpin structure of the non-template DNA strand

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Philipp K Zuber ◽  
Irina Artsimovitch ◽  
Monali NandyMazumdar ◽  
Zhaokun Liu ◽  
Yuri Nedialkov ◽  
...  
Keyword(s):  
Virulence Genes ◽  
Complex Structure ◽  
Transcription Regulator ◽  
Transcription Bubble ◽  
Template Strand ◽  
Domains Of Life ◽  
Dna Strand ◽  
Functional Analyses ◽  
Template Dna

RfaH, a transcription regulator of the universally conserved NusG/Spt5 family, utilizes a unique mode of recruitment to elongating RNA polymerase to activate virulence genes. RfaH function depends critically on an ops sequence, an exemplar of a consensus pause, in the non-template DNA strand of the transcription bubble. We used structural and functional analyses to elucidate the role of ops in RfaH recruitment. Our results demonstrate that ops induces pausing to facilitate RfaH binding and establishes direct contacts with RfaH. Strikingly, the non-template DNA forms a hairpin in the RfaH:ops complex structure, flipping out a conserved T residue that is specifically recognized by RfaH. Molecular modeling and genetic evidence support the notion that ops hairpin is required for RfaH recruitment. We argue that both the sequence and the structure of the non-template strand are read out by transcription factors, expanding the repertoire of transcriptional regulators in all domains of life.

scholarly journals Role of Mitochondrial Cytochrome P450 2E1 in Healthy and Diseased Liver

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 288
Author(s):  
Julie Massart ◽  
Karima Begriche ◽  
Jessica H. Hartman ◽  
Bernard Fromenty
Keyword(s):  
Oxidative Stress ◽  
Cytochrome P450 ◽  
Liver Disease ◽  
Fatty Liver ◽  
Current Knowledge ◽  
Physiological Role ◽  
Experimental Investigations ◽  
Rat Liver Mitochondria ◽  
Cytochrome P450 2E1

Cytochrome P450 2E1 (CYP2E1) is pivotal in hepatotoxicity induced by alcohol abuse and different xenobiotics. In this setting, CYP2E1 generates reactive metabolites inducing oxidative stress, mitochondrial dysfunction and cell death. In addition, this enzyme appears to play a role in the progression of obesity-related fatty liver to nonalcoholic steatohepatitis. Indeed, increased CYP2E1 activity in nonalcoholic fatty liver disease (NAFLD) is deemed to induce reactive oxygen species overproduction, which in turn triggers oxidative stress, necroinflammation and fibrosis. In 1997, Avadhani’s group reported for the first time the presence of CYP2E1 in rat liver mitochondria, and subsequent investigations by other groups confirmed that mitochondrial CYP2E1 (mtCYP2E1) could be found in different experimental models. In this review, we first recall the main features of CYP2E1 including its role in the biotransformation of endogenous and exogenous molecules, the regulation of its expression and activity and its involvement in different liver diseases. Then, we present the current knowledge on the physiological role of mtCYP2E1, its contribution to xenobiotic biotransformation as well as the mechanism and regulation of CYP2E1 targeting to mitochondria. Finally, we discuss experimental investigations suggesting that mtCYP2E1 could have a role in alcohol-associated liver disease, xenobiotic-induced hepatotoxicity and NAFLD.

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