Genome - nuclear lamina interactions are multivalent and cooperative DOI Creative Commons
Lise Dauban, M Eder,

Marcel de Haas

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 10, 2024

Abstract Lamina-associated domains (LADs) are megabase-sized genomic regions that interact with the nuclear lamina (NL). It is not yet understood how their interactions NL encoded in DNA. Here, we designed an efficient LAD “scrambling” approach, based on transposon-mediated local hopping of loxP recombination sites, to generate series large deletions and inversions span LADs flanking sequences. Mapping these rearrangements revealed a single contacts through multiple act cooperatively or redundantly; some have more affinity for than others can pull neighbouring sequences NL. Genes drawn towards showed often, but always, reduced expression increased H3K9me3 levels. Furthermore, when placed close enough each other. These results elucidate principles govern positioning inside cell nucleus. Highlights Efficient generation by transposon elements. multivalent, subregions being potent tethers others. cooperate promote association Changes often accompanied changes gene activity H3K9me3.

Language: Английский

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

Martín Stortz,

Diego M. Presman, Valeria Levi

et al.

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Feb. 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.

Language: Английский

Citations

26
Mesoscale phase separation of chromatin in the nucleus DOI Creative Commons
Gaurav Bajpai, Daria Amiad Pavlov, Dana Lorber

et al.

eLife, Journal Year: 2021, Volume and Issue: 10

Published: May 4, 2021

Intact-organism imaging of Drosophila larvae reveals and quantifies chromatin-aqueous phase separation. The chromatin can be organized near the lamina layer nuclear envelope, conventionally fill nucleus, centrally, or as a wetting droplet. These transitions are controlled by changes in volume interaction with (part envelope) at periphery. Using simple polymeric model that includes key features self-attraction its binding to lamina, we demonstrate theoretically it is competition these two effects determines mode distribution. qualitative trends well composition profiles obtained our simulations compare observed intact-organism quantification. Since contain only small number physical variables identify generic mechanisms underlying separations.

Language: Английский

Citations

70
Balance of osmotic pressures determines the nuclear-to-cytoplasmic volume ratio of the cell DOI Creative Commons
Dan Deviri, S. A. Safran

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(21)

Published: May 17, 2022

The volume of the cell nucleus varies across types and species is commonly thought to be determined by size genome degree chromatin compaction. However, this notion has been challenged over years much experimental evidence. Here, we consider physical condition mechanical force balance as a determining nuclear use quantitative, order-of-magnitude analysis estimate forces from different sources cytoplasmic pressure. Our estimates suggest that dominant pressure within cytoplasm nonstriated muscle cells originates osmotic proteins RNA molecules are localized or out-of-equilibrium, active nucleocytoplasmic transport rather than its associated ions. This motivates us formulate model for ratio volumes in which pressures determine relative volumes. In accordance with unexplained observations century old, our predicts constant, robust wide variety biochemical biophysical manipulations, changed only if gene expression modulated.

Language: Английский

Citations

55
Shaping the genome via lengthwise compaction, phase separation, and lamina adhesion DOI Creative Commons
Sumitabha Brahmachari, Vinícius G. Contessoto, Michele Di Pierro

et al.

Nucleic Acids Research, Journal Year: 2022, Volume and Issue: 50(8), P. 4258 - 4271

Published: April 14, 2022

Abstract The link between genomic structure and biological function is yet to be consolidated, it is, however, clear that physical manipulation of the genome, driven by activity a variety proteins, crucial step. To understand consequences forces underlying genome organization, we build coarse-grained polymer model featuring three fundamentally distinct classes interactions: lengthwise compaction, i.e., compaction chromosomes along its contour, self-adhesion among epigenetically similar segments, adhesion chromosome segments nuclear envelope or lamina. We postulate these types interactions sufficiently represent concerted action different proteins organizing architecture show an interplay can recapitulate architectural variants observed across tree life. elucidates how arising from drive drastic, predictable, changes in global architecture, makes testable predictions. posit precise control over vivo key regulation architecture.

Language: Английский

Citations

44
Chromatin reprogramming and bone regeneration in vitro and in vivo via the microtopography-induced constriction of cell nuclei DOI
Xinlong Wang, Vasundhara Agrawal,

Cody L. Dunton

et al.

Nature Biomedical Engineering, Journal Year: 2023, Volume and Issue: 7(11), P. 1514 - 1529

Published: June 12, 2023

Language: Английский

Citations

39
Compartmentalization with nuclear landmarks yields random, yet precise, genome organization DOI Creative Commons
Kartik Kamat,

Zhuohan Lao,

Yifeng Qi

et al.

Biophysical Journal, Journal Year: 2023, Volume and Issue: 122(7), P. 1376 - 1389

Published: March 5, 2023

Language: Английский

Citations

27
Predicting scale-dependent chromatin polymer properties from systematic coarse-graining DOI Creative Commons
Sangram Kadam, Kiran Kumari, Vinoth Manivannan

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 11, 2023

Simulating chromatin is crucial for predicting genome organization and dynamics. Although coarse-grained bead-spring polymer models are commonly used to describe chromatin, the relevant bead dimensions, elastic properties, nature of inter-bead potentials unknown. Using nucleosome-resolution contact probability (Micro-C) data, we systematically coarse-grain predict quantities essential representation chromatin. We compute size distributions beads different coarse-graining scales, quantify fluctuations bond lengths between neighboring regions, derive effective spring constant values. Unlike prevalent notion, our findings argue that must be considered as soft particles can overlap, an potential overlap parameter. also angle giving insights into intrinsic folding local bendability While nucleosome-linker DNA naturally emerges from work, show two populations structural states. The sizes, lengths, angles mean behavior at Topologically Associating Domain (TAD) boundaries TAD interiors. integrate a model provide quantitative estimates all parameters, which serve foundational basis future simulations.

Language: Английский

Citations

26
Regulation of chromatin microphase separation by binding of protein complexes DOI Creative Commons
Omar Adame-Arana, Gaurav Bajpai, Dana Lorber

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: July 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.

Language: Английский

Citations

25
True-to-scale DNA-density maps correlate with major accessibility differences between active and inactive chromatin DOI Creative Commons
Márton Gelléri,

Shih‐Ya Chen,

Barbara Hübner

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(6), P. 112567 - 112567

Published: May 26, 2023

Chromatin compaction differences may have a strong impact on accessibility of individual macromolecules and macromolecular assemblies to their DNA target sites. Estimates based fluorescence microscopy with conventional resolution, however, suggest only modest (∼2-10×) between the active nuclear compartment (ANC) inactive (INC). Here, we present maps landscapes true-to-scale densities, ranging from <5 >300 Mbp/μm3. Maps are generated human mouse cell nuclei single-molecule localization at ∼20 nm lateral ∼100 axial optical resolution supplemented by electron spectroscopic imaging. Microinjection fluorescent nanobeads sizes corresponding for transcription into living cells demonstrates movements within ANC exclusion INC.

Language: Английский

Citations

24
From Nucleosomes to Compartments: Physicochemical Interactions Underlying Chromatin Organization DOI
Shuming Liu, Advait Athreya,

Zhuohan Lao

et al.

Annual Review of Biophysics, Journal Year: 2024, Volume and Issue: 53(1), P. 221 - 245

Published: Feb. 12, 2024

Chromatin organization plays a critical role in cellular function by regulating access to genetic information. However, understanding chromatin folding is challenging due its complex, multiscale nature. Significant progress has been made studying vitro systems, uncovering the structure of individual nucleosomes and their arrays, elucidating physicochemical forces stabilizing these structures. Additionally, remarkable advancements have achieved characterizing vivo, particularly at whole-chromosome level, revealing important features such as loops, topologically associating domains, nuclear compartments. bridging gap between vivo studies remains challenging. The resemblance conformations relevance internucleosomal interactions for are subjects debate. This article reviews experimental computational conducted various length scales, highlighting significance intrinsic roles vivo.

Language: Английский

Citations

15