Real-time single-molecule imaging of transcriptional regulatory networks in living cells

Nature Reviews Genetics, Год журнала: 2024, Номер 25(4), С. 272 - 285

Опубликована: Янв. 9, 2024

Язык: Английский

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RNA: The Unsuspected Conductor in the Orchestra of Macromolecular Crowding

Chemical Reviews, Год журнала: 2024, Номер 124(8), С. 4734 - 4777

Опубликована: Апрель 5, 2024

This comprehensive Review delves into the chemical principles governing RNA-mediated crowding events, commonly referred to as granules or biological condensates. We explore pivotal role played by RNA sequence, structure, and modifications in these processes, uncovering their correlation with phenomena under physiological conditions. Additionally, we investigate instances where deviates from its intended function, leading pathological consequences. By deepening our understanding of delicate balance that governs molecular driven implications for cellular homeostasis, aim shed light on this intriguing area research. Our exploration extends methodologies employed decipher composition structural intricacies granules, offering a overview techniques used characterize them, including relevant computational approaches. Through two detailed examples highlighting significance noncoding RNAs, NEAT1 XIST, formation phase-separated assemblies influence landscape, emphasize crucial organization function. elucidating underpinnings crowding, investigating modifications, structures, exploring both aberrant phase separation phenomena, provides multifaceted world

Язык: Английский

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Lifelong persistence of nuclear RNAs in the mouse brain

Science, Год журнала: 2024, Номер 384(6691), С. 53 - 59

Опубликована: Апрель 4, 2024

Genomic DNA that resides in the nuclei of mammalian neurons can be as old organism itself. The life span nuclear RNAs, which are critical for proper chromatin architecture and transcription regulation, has not been determined adult tissues. In this work, we identified characterized RNAs do turn over at least 2 years a subset postnatally born cells mouse brain. These long-lived were stably retained neural cell type–specific manner required maintenance heterochromatin. Thus, may depend on both molecular longevity storage genetic information also extreme stability RNA functional organization chromatin.

Язык: Английский

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Evolution and regulation of animal sex chromosomes

Nature Reviews Genetics, Год журнала: 2024, Номер unknown

Опубликована: Июль 18, 2024

Язык: Английский

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Nitric oxide inhibits ten-eleven translocation DNA demethylases to regulate 5mC and 5hmC across the genome

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 18, 2025

DNA methylation at cytosine bases (5-methylcytosine, 5mC) is a heritable epigenetic mark regulating gene expression. While enzymes that metabolize 5mC are well-characterized, endogenous signaling molecules regulate machinery have not been described. We report physiological nitric oxide (NO) concentrations reversibly inhibit the demethylases TET and ALKBH2 by binding to mononuclear non-heme iron atom forming dinitrosyliron complex (DNIC) preventing cosubstrates from binding. In cancer cells treated with exogenous NO, or endogenously synthesizing 5-hydroxymethylcytosine (5hmC) increase, no changes in methyltransferase activity. also significantly increased NO-producing patient-derived xenograft tumors mice. Genome-wide methylome analysis of chronically NO (10 days) shows enrichment 5hmC gene-regulatory loci, correlating altered expression NO-regulated tumor-associated genes. Regulation distinctly different canonical represents unique role for NO.

Язык: Английский

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Estrogen influences class-switched memory B cell frequency only in humans with two X chromosomes

The Journal of Experimental Medicine, Год журнала: 2025, Номер 222(4)

Опубликована: Март 6, 2025

Sex differences in immunity are well-documented, though mechanisms underpinning these remain ill-defined. Here, a human-only ex vivo study, we demonstrate that postpubertal cisgender females have higher levels of CD19+CD27+IgD− class-switched memory B cells compared with age-matched males. This increase is only observed after puberty and before menopause, suggesting strong influence for sex hormones. Accordingly, express high estrogen receptor 2 (ESR2), class-switch–regulating genes enriched ESR2-binding sites. In gender-diverse cohort, blockade natal transgender males (XX karyotype) reduced cell frequency, while gender-affirming estradiol treatment (XY did not levels. postmenopausal cis-females, were increased those taking hormone replacement therapy (HRT) who not. These data hormones chromosomes work tandem to impact immune responses, influencing the frequency individuals an XX chromosomal background.

Язык: Английский

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Transcriptional stochasticity reveals multiple mechanisms of long non-coding RNA regulation at the Xist – Tsix locus

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 5, 2025

ABSTRACT Long noncoding RNAs (LncRNAs) are increasingly recognized as being involved in human physiology and diseases, but there is a lack of mechanistic understanding for the majority lncRNAs. We comparatively tested proposed mechanisms antisense lncRNA regulation at X-chromosome Inactivation (XCI) locus. find that due to stochasticity transcription, different based on act transcription regulate Xist Tsix levels nascent transcription. At medium levels, RNA polymerases transcribe each strand same site deposit significant amounts histone mark H3K36me3, which inhibits Xist. high many or resulting transcriptional interference. Therefore, expression variability not just quirk an important aspect allows multiple be employed by gene locus within cell population.

Язык: Английский

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Beyond equilibrium: roles of RNAs in condensate control

Current Opinion in Genetics & Development, Год журнала: 2025, Номер 91, С. 102304 - 102304

Опубликована: Янв. 14, 2025

Membraneless subcompartments organize various activities in the cell nucleus. Some of them are formed through phase separation that is driven by polymeric and multivalent nature biomolecules. Here, we discuss role RNAs regulating nuclear subcompartments. On one hand, chromatin-associated RNA molecules may act as binding platforms recruit to specific genomic loci. other scaffolds stabilize biomolecular condensates. The active production processing inside drives out thermodynamic equilibrium thereby modulates their properties. Accordingly, content transcriptional activity appear key determinants biophysical functional substructures.

Язык: Английский

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Temporal and regional X-linked gene reactivation in the mouse germline reveals site-specific retention of epigenetic silencing

Nature Structural & Molecular Biology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 21, 2025

Язык: Английский

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Reconstruction of diploid higher-order human 3D genome interactions from noisy Pore-C data using Dip3D

Nature Structural & Molecular Biology, Год журнала: 2025, Номер unknown

Опубликована: Март 4, 2025

Язык: Английский

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