Immediate perturbation of DNA methylation upon acute prenatal alcohol exposure in the mouse developing brain cortex DOI Creative Commons

Agathe Duchateau,

Carole Chaput,

Lea Livramento

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: March 10, 2022

Abstract The reshaping of the DNA methylome landscape after prenatal alcohol exposure (PAE) has been well-documented in adult brain, therefore a long time end exposure. However, question immediate deposition or loss methylation marks neocortex, just PAE not yet directly addressed, genome widely. Using binge-drinking-like model and capture methylome, we have identified differentially methylated regions (DMRs) that are established immediately, within two hours PAE. Remarkably, these DMRs prominently statistically associated with: (i) enhancers active with GO terms importance for neurogenesis, neurodevelopment, neuronal differentiation; (ii) genes that, physiological conditions show dynamic gain chromatin accessibility and/or upregulation their expression time-window exposure; (iii) imprinted members protocadherin clusters, gene families playing key roles whose mono-allelically is regulated by impaired upon We observed DMR-containing expressed genes, as well other important also immediately upregulated PAE, suggesting early perturbations thus highly susceptible to rapidly alter previously identified, both rodent brain prior-exposed prenatally, cohorts children diagnosed fetal spectrum disorders (FASD). Our study strongly suggests profiles regulatory very quickly disturbed altered could be persistently affected stress. This reinforces potential future biomarkers In addition, provokes rewiring transcriptome potentially dual consequences: 1) beneficial impacts support recovery cells from exposure, through slowing down protein synthesis energy-consuming respiratory pathways; 2) detrimental effects, inappropriate activation critical pathways may perturb neurodevelopment. Ethical issues breeding treatments wild type C57BL/6N mice, used experimental protocols described this approved Institutional Animal Care Use Committee Paris Cité University (registration number CEEA-40). project recorded under following reference Ministère de l’Enseignement Supérieur et la Recherche (#2016040414515579). All efforts were made reduce stress pain animals.

Language: Английский

Molecular determinants of condensate composition DOI Creative Commons
Alex S. Holehouse, Simon Alberti

Molecular Cell, Journal Year: 2025, Volume and Issue: 85(2), P. 290 - 308

Published: Jan. 1, 2025

Language: Английский

Citations

4
Polysome collapse and RNA condensation fluidize the cytoplasm DOI
Ying Xie, Tong Shu,

Tiewei Liu

et al.

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(14), P. 2698 - 2716.e9

Published: July 1, 2024

Language: Английский

Citations

9
A thermosensor FUST1 primes heat-induced stress granule formation via biomolecular condensation in Arabidopsis DOI Creative Commons
Pan Geng, Changxuan Li, Xuebo Quan

et al.

Cell Research, Journal Year: 2025, Volume and Issue: unknown

Published: May 14, 2025

Language: Английский

Citations

1
Heat Shock Factor 1 forms nuclear condensates and restructures the yeast genome before activating target genes DOI Creative Commons
Linda S Rubio, Suman Mohajan, David S. Gross

et al.

eLife, Journal Year: 2024, Volume and Issue: 12

Published: Oct. 15, 2024

In insects and mammals, 3D genome topology has been linked to transcriptional states yet whether this link holds for other eukaryotes is unclear. Using both ligation proximity fluorescence microscopy assays, we show that in Saccharomyces cerevisiae , Heat Shock Response ( HSR ) genes dispersed across multiple chromosomes under the control of Factor (Hsf1) rapidly reposition cells exposed acute ethanol stress engage concerted, Hsf1-dependent intergenic interactions. Accompanying reconfiguration equally rapid formation Hsf1-containing condensates. However, contrast transience Hsf1-driven interactions peak within 10–20 min dissipate 1 hr presence 8.5% (v/v) ethanol, condensates are stably maintained hours. Moreover, same conditions, Pol II occupancy genes, chromatin remodeling, RNA expression detectable only later response much (>1 hr). This contrasts with coordinate thermal (39°C) where occupancy, transcription, histone eviction, interactions, Hsf1 all transient (peak 2.5–10 Therefore, forms condensates, restructures transcriptionally activates proteotoxic but does so strikingly different kinetics. subjected stress, repositions target before activating them.

Language: Английский

Citations

5
tRNA synthetase activity is required for stress granule and P-body assembly DOI Creative Commons
Max Baymiller, Noah S. Helton,

Benjamin Dodd

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

In response to stress, translation initiation is suppressed and ribosome runoff via elongation drives mRNA assembly into ribonucleoprotein (RNP) granules including stress P-bodies. Defects in activate the integrated response. If how stalled ribosomes are removed from mRNAs during drive RNP granule not clear. We demonstrate induced upon tRNA synthetase inhibition part collision sensing. However, saturating levels of inhibitors do induce or P-bodies prevent exogenous stress. The loss activity causes persistent stalls that can be released with puromycin but rescued by ribosome-associated quality control pathways. Therefore, required for run off scaffold cytoplasmic granules. Our findings suggest persist human cells uniquely uncouple condensate

Language: Английский

Citations

0
Molecular mechanisms underlying the evolution of a color polyphenism by genetic accommodation in the tobacco hornworm, Manduca sexta DOI Creative Commons
Yuichiro Suzuki,

Stephanie Amaya,

Paula González

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(12)

Published: March 19, 2025

How organisms evolve under extreme environmental changes is a critical question in the face of global climate change. Genetic accommodation an evolutionary process by which natural selection acts on novel phenotypes generated through repeated encounters with environments. In this study, polyphenic and monophenic strains black mutant tobacco hornworm, Manduca sexta , were evolved via genetic heat stress-induced phenotypes, molecular differences between two explored. Transcriptomic analyses showed that epigenetic hormonal underlie their distinct responses to temperature. DNA methylation had diverged potentially mediating assimilation. Juvenile hormone (JH) signaling strain was temperature sensitive, whereas strain, JH remained low at all temperatures. Although 20-hydroxyecdysone titers elevated shock conditions both strains, did not differ titers. Tyrosine hydroxylase also found different temperatures, its expression could be modulated topical application analog. Finally, unselected mutants demonstrated JH-response gene, Krüppel-homolog 1 ( Kr-h1 ), increased within first 30 min shock, suggesting levels respond readily thermal stress. Our study highlights role hormones epigenetics play during evolution populations

Language: Английский

Citations

0
Selective Translation Under Heat Shock: Integrating HSP70 mRNA Regulation with Cellular Stress Responses in Yeast and Mammals DOI

Talar Ghadanian,

Shruti Iyer, Luca Lazzari

et al.

Molecular Biology of the Cell, Journal Year: 2025, Volume and Issue: 36(5)

Published: April 8, 2025

Under stress, cells orchestrate a complex regulatory response to maintain protein homeostasis, leveraging differential translational regulation for constitutively expressed mRNAs and the transcriptionally induced heat shock HSP70 transcripts. Constitutive typically experience partial suppression, consistent with their partitioning into stress-induced phase-separated condensates global reduction in synthesis. In contrast, inducible bypass this repression remain cytosol where they recruit available components of machinery ensure rapid synthesis HSP70. Although involved preferential translation mRNA during stress have not been fully elucidated, differences factors between yeast mammals suggest organism-specific mechanisms translation. review, we consider these discuss current knowledge on We extend discussion go beyond cytosolic needs ponder important interplay mitochondria activating accumulation, which becomes vital preserving intercompartmental proteostasis cell survival.

Language: Английский

Citations

0
Surviving the heat: the role of macromolecular assemblies in promoting cellular shutdown DOI Creative Commons
Christine Desroches Altamirano, Simon Alberti

Trends in Biochemical Sciences, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

3
Heat Shock Factor 1 forms condensates and restructures the yeast genome before activating target genes DOI Open Access
Linda S Rubio, Suman Mohajan, David S. Gross

et al.

Published: Aug. 8, 2024

In insects and mammals, 3D genome topology has been linked to transcriptional states yet whether this link holds for other eukaryotes is unclear. Using both ligation proximity fluorescence microscopy assays, we show that in Saccharomyces cerevisiae , Heat Shock Response ( HSR ) genes dispersed across multiple chromosomes under the control of Factor (Hsf1) rapidly reposition cells exposed acute ethanol stress engage concerted, Hsf1-dependent intergenic interactions. Accompanying reconfiguration equally rapid formation Hsf1-containing condensates. However, contrast transience Hsf1-driven interactions peak within 10-20 min dissipate 1 h presence 8.5% (v/v) ethanol, condensates are stably maintained hours. Moreover, same conditions, Pol II occupancy RNA expression detectable only later response much (>1 h). This contrasts with coordinate thermal (39°C) where occupancy, transcription, interactions, Hsf1 all transient (peak 2.5-10 Therefore, forms condensates, restructures transcriptionally activates proteotoxic but does so strikingly different kinetics. subjected stress, repositions target before activating them.

Language: Английский

Citations

1
Protocol to reconstitute translationally arrested heat shock mRNPs and condensates in vitro DOI Creative Commons
Christine Desroches Altamirano, Simon Alberti

STAR Protocols, Journal Year: 2024, Volume and Issue: 5(3), P. 103275 - 103275

Published: Aug. 23, 2024

Heat shock (HS) coincides with the assembly of translationally arrested heat messenger ribonucleoprotein particles (HS-mRNPs) and condensates. Here, we present a protocol to reconstitute HS-mRNPs HS condensates eIF4G, eIF4E, Pab1p, mRNA in vitro. In addition, describe necessary steps measure effect on translation yeast extracts. The can be modified study mRNPs assembled other proteins extracts prepared from different cells. For complete details use execution this protocol, please refer Desroches Altamirano et al.

Language: Английский

Citations

1