Transcriptionally active chromatin loops contain both ‘active’ and ‘inactive’ histone modifications that exhibit exclusivity at the level of nucleosome clusters DOI Creative Commons
Stefan A. Koestler, Madeleine L. Ball, Leila Mureşan

и другие.

Epigenetics & Chromatin, Год журнала: 2024, Номер 17(1)

Опубликована: Март 25, 2024

Abstract Chromatin state is thought to impart regulatory function the underlying DNA sequence. This can be established through histone modifications and chromatin organisation, but exactly how these factors relate one another regulate gene expression unclear. In this study, we have used super-resolution microscopy image Y loops of Drosophila melanogaster primary spermatocytes, which are enormous transcriptionally active fibres, each representing single transcription units that individually resolvable in nuclear interior. We previously found consist regular clusters nucleosomes, with an estimated median 54 nucleosomes per cluster wide variation. report H3K4me3, H3K27me3, H3K36me3 also clustered along loops, H3K4me3 more associated diffuse compared H3K27me3. These form domains stretches loop micrometres long, or short alternating domains. The different sizes unique morphologies. Strikingly, a almost always only contains type were labelled, suggesting exclusivity, therefore regulation at level individual clusters. mark actively elongating RNA polymerase II than often appearing on what assumed looping regions periphery results provide foundation for understanding relationship between state, – potential implications pause-release dynamics, splicing complex organisation dynamics during progression gene.

Язык: Английский

Sequence-dependent surface condensation of a pioneer transcription factor on DNA DOI Creative Commons
José A. Morín, Sina Wittmann, Sandeep Choubey

и другие.

Nature Physics, Год журнала: 2022, Номер 18(3), С. 271 - 276

Опубликована: Фев. 3, 2022

Abstract Biomolecular condensates are dense assemblies of proteins that form distinct biochemical compartments without being surrounded by a membrane. Some, such as P granules and stress granules, behave droplets contain many millions molecules. Others, transcriptional on the surface DNA, small thousands The physics behind formation DNA surfaces is still under discussion. Here we investigate nature transcription factor using pioneer Krüppel-like 4 (Klf4). We show Klf4 can phase separate its own at high concentrations, but low only forms DNA. Using optical tweezers, demonstrate these type condensation. This condensation involves switch-like transition from thin adsorbed layer to thick condensed layer, which shows hallmarks prewetting transition. localization correlates with sequence, suggesting condensate sequence-dependent Prewetting together sequence specificity explain size position control condensates. speculate factors underlies positioning provides robustness regulation.

Язык: Английский

Процитировано

127
RNA polymerase II dynamics shape enhancer–promoter interactions DOI
Gilad Barshad, James J. Lewis, Alexandra G. Chivu

и другие.

Nature Genetics, Год журнала: 2023, Номер 55(8), С. 1370 - 1380

Опубликована: Июль 10, 2023

Язык: Английский

Процитировано

78
Transcriptional condensates: a blessing or a curse for gene regulation? DOI Creative Commons

Martín Stortz,

Diego M. Presman, Valeria Levi

и другие.

Communications Biology, Год журнала: 2024, Номер 7(1)

Опубликована: Фев. 16, 2024

Whether phase-separation is involved in the organization of transcriptional machinery and if it aids or inhibits process a matter intense debate. In this Mini Review, we will cover current knowledge regarding role condensates on gene expression regulation. We summarize latest discoveries relationship between condensate formation, genome organization, activity, focusing strengths weaknesses experimental approaches used to interrogate these aspects transcription living cells. Finally, discuss challenges for future research.

Язык: Английский

Процитировано

27
RNA polymerase II clusters form in line with surface condensation on regulatory chromatin DOI
Agnieszka Pancholi, Tim Klingberg, Weichun Zhang

и другие.

Molecular Systems Biology, Год журнала: 2021, Номер 17(9)

Опубликована: Сен. 1, 2021

Язык: Английский

Процитировано

64
Rheology and Viscoelasticity of Proteins and Nucleic Acids Condensates DOI Creative Commons
Davide Michieletto, Mattia Marenda

JACS Au, Год журнала: 2022, Номер 2(7), С. 1506 - 1521

Опубликована: Июнь 13, 2022

Phase separation is as familiar watching vinegar separating from oil in vinaigrette. The observation that phase of proteins and nucleic acids widespread living cells has opened an entire field research into the biological significance biophysical mechanisms protein condensation biology. Recent evidence indicates certain condensates are not simple liquids instead display both viscous elastic behaviors, which turn may have significance. aim this Perspective to review state-of-the-art quickly emerging focusing on material rheological properties condensates. Finally, we discuss different techniques can be employed quantify viscoelasticity highlight potential future directions opportunities for interdisciplinary cross-talk between chemists, physicists, biologists.

Язык: Английский

Процитировано

61
Mesoscale structure–function relationships in mitochondrial transcriptional condensates DOI Creative Commons
Marina Feric,

Azadeh Sarfallah,

Furqan Dar

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2022, Номер 119(41)

Опубликована: Окт. 3, 2022

In live cells, phase separation is thought to organize macromolecules into membraneless structures known as biomolecular condensates. Here, we reconstituted transcription in condensates from purified mitochondrial components using optimized vitro reaction conditions probe the structure–function relationships of We find that core mt-transcription machinery form multiphasic, viscoelastic vitro. Strikingly, rates condensate-mediated are substantially lower than solution. The decrease transcriptional associated with formation vesicle-like driven by production and accumulation RNA during transcription. generation alters global behavior organization within Coarse-grained simulations mesoscale at equilibrium show stably assemble multiphasic vesicles formed result dynamical arrest. Overall, our findings illustrate complex transcribing, multicomponent condensates, they highlight intimate, bidirectional interplay structure function

Язык: Английский

Процитировано

49
HP1-driven phase separation recapitulates the thermodynamics and kinetics of heterochromatin condensate formation DOI Creative Commons
Maxime M. C. Tortora, Lucy D. Brennan, Gary H. Karpen

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(33)

Опубликована: Авг. 7, 2023

The spatial segregation of pericentromeric heterochromatin (PCH) into distinct, membrane-less nuclear compartments involves the binding Heterochromatin Protein 1 (HP1) to H3K9me2/3-rich genomic regions. While HP1 exhibits liquid–liquid phase separation properties in vitro, its mechanistic impact on structure and dynamics PCH condensate formation vivo remains largely unresolved. Here, using a minimal theoretical framework, we systematically investigate mutual coupling between self-interacting HP1-like molecules chromatin polymer. We reveal that specific affinity for H3K9me2/3 loci facilitates coacervation nucleo promotes stable condensates at levels far below concentration required observe purified protein assays vitro. These heterotypic HP1–chromatin interactions give rise strong dependence nucleoplasmic density HP1-H3K9me2/3 stoichiometry, consistent with thermodynamics multicomponent separation. dynamical cross talk viscoelastic scaffold also leads anomalously slow equilibration kinetics, which strongly depend distribution domains result coexistence multiple long-lived, microphase-separated compartments. morphology these complex coacervates is further found be governed by dynamic establishment underlying landscape, may drive their increasingly abnormal, aspherical shapes during cell development. findings compare favorably 4D microscopy measurements live Drosophila embryos suggest general quantitative model based interplay HP1-based polymer mechanics.

Язык: Английский

Процитировано

29
Regulation of chromatin microphase separation by binding of protein complexes DOI Creative Commons
Omar Adame-Arana, Gaurav Bajpai, Dana Lorber

и другие.

eLife, Год журнала: 2023, Номер 12

Опубликована: Июль 12, 2023

We show evidence of the association RNA polymerase II (RNAP) with chromatin in a core-shell organization, reminiscent microphase separation where cores comprise dense and shell, RNAP low density. These observations motivate our physical model for regulation organization. Here, we as multiblock copolymer, comprising active inactive regions (blocks) that are both poor solvent tend to be condensed absence binding proteins. However, quality can regulated by protein complexes (e.g., transcription factors). Using theory polymer brushes, find such leads swelling which turn modifies spatial organization regions. In addition, use simulations study spherical micelles, whose shells bound complexes. micelles increases number controls their size. Thus, genetic modifications affecting strength chromatin-binding may modulate experienced regulate genome.

Язык: Английский

Процитировано

26
Compartmentalization of the SUMO/RNF4 pathway by SLX4 drives DNA repair DOI Open Access
Emile Alghoul, Matteo Paloni, Arato Takedachi

и другие.

Molecular Cell, Год журнала: 2023, Номер 83(10), С. 1640 - 1658.e9

Опубликована: Апрель 13, 2023

Язык: Английский

Процитировано

25
Dynamic microenvironments shape nuclear organization and gene expression DOI Creative Commons
Gabriela Hayward-Lara, Matthew D. Fischer, Mustafa Mir

и другие.

Current Opinion in Genetics & Development, Год журнала: 2024, Номер 86, С. 102177 - 102177

Опубликована: Март 11, 2024

Язык: Английский

Процитировано

11