Fundamental Aspects of Phase-Separated Biomolecular Condensates

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(13), P. 8550 - 8595

Published: June 17, 2024

Biomolecular condensates, formed through phase separation, are upending our understanding in much of molecular, cell, and developmental biology. There is an urgent need to elucidate the physicochemical foundations behaviors properties biomolecular condensates. Here we aim fill this by writing a comprehensive, critical, accessible review on fundamental aspects phase-separated We introduce relevant theoretical background, present basis for computation experimental measurement condensate properties, give mechanistic interpretations terms interactions at molecular residue levels.

Language: Английский

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Human neuronal maturation comes of age: cellular mechanisms and species differences

Nature reviews. Neuroscience, Journal Year: 2023, Volume and Issue: 25(1), P. 7 - 29

Published: Nov. 23, 2023

Language: Английский

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Droplet Hi-C enables scalable, single-cell profiling of chromatin architecture in heterogeneous tissues

Nature Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 18, 2024

Abstract Current methods for analyzing chromatin architecture are not readily scalable to heterogeneous tissues. Here we introduce Droplet Hi-C, which uses a commercial microfluidic device high-throughput, single-cell conformation profiling in droplets. Using mapped the of mouse cortex and analyzed gene regulatory programs major cortical cell types. In addition, used this technique detect copy number variations, structural variations extrachromosomal DNA human glioblastoma, colorectal blood cancer cells, revealing clonal dynamics other oncogenic events during treatment. We refined allow joint transcriptome single facilitating exploration links between expression both normal tissues tumors. Thus, Hi-C addresses critical gaps analysis enhances understanding regulation.

Language: Английский

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Chromosome structure in Drosophila is determined by boundary pairing not loop extrusion

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Feb. 5, 2024

Two different models have been proposed to explain how the endpoints of chromatin looped domains (‘TADs’) in eukaryotic chromosomes are determined. In first, a cohesin complex extrudes loop until it encounters boundary element roadblock, generating stem-loop. this model, boundaries functionally autonomous: they an intrinsic ability halt movement incoming complexes that is independent properties neighboring boundaries. second, loops generated by boundary:boundary pairing. non-autonomous, and their form depends upon well match with neighbors. Moreover, unlike loop-extrusion pairing interactions can generate both stem-loops circle-loops. We used combination MicroC analyze TADs organized, experimental manipulations even skipped TAD boundary, homie , test predictions ‘loop-extrusion’ ‘boundary-pairing’ models. Our findings incompatible instead suggest flies determined mechanism which elements physically pair partners, either head-to-head or head-to-tail, varying degrees specificity. Although our experiments do not address partners find each other, unlikely require extrusion.

Language: Английский

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Chromatin compaction by Polycomb group proteins revisited

Current Opinion in Structural Biology, Journal Year: 2024, Volume and Issue: 86, P. 102806 - 102806

Published: March 27, 2024

The chromatin compaction activity of Polycomb group proteins has traditionally been considered essential for transcriptional repression. However, there is very little information on how compact at the molecular level and no causal link between compactness Recently, a more complete picture Polycomb-dependent architecture started to emerge, owing advanced methods imaging chromosome conformation capture. Discoveries into Polycomb-driven phase separation add another layer complexity. Recent observations generally imply that modulate structure multiple scales reduce its dynamics segregate it from active domains. Hence, reasonable hypothesise maintain energetically favourable state compacted chromatin, rather than actively it.

Language: Английский

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Chromosome fusion and programmed DNA elimination shape karyotypes of nematodes

Current Biology, Journal Year: 2024, Volume and Issue: 34(10), P. 2147 - 2161.e5

Published: April 29, 2024

Language: Английский

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Mechanisms of sex determination and X-chromosome dosage compensation

Genetics, Journal Year: 2022, Volume and Issue: 220(2)

Published: Jan. 6, 2022

Abstract Abnormalities in chromosome number have the potential to disrupt balance of gene expression and thereby decrease organismal fitness viability. Such abnormalities occur most solid tumors also cause severe developmental defects spontaneous abortions. In contrast imbalances dose that pathologies, difference X-chromosome used determine sexual fate across diverse species is well tolerated. Dosage compensation mechanisms evolved such between sexes, allowing them tolerate dose. This review analyzes counting mechanism tallies sex (XO male XX hermaphrodite) nematode Caenorhabditis elegans associated dosage balances sexes. Dissecting molecular underlying has revealed how small quantitative differences intracellular signals can be translated into dramatically different fates. process interplay chromatin modification structure regulating over vast chromosomal territories.

Language: Английский

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SATB1 regulates 3D genome architecture in T cells by constraining chromatin interactions surrounding CTCF-binding sites

Cell Reports, Journal Year: 2023, Volume and Issue: 42(4), P. 112323 - 112323

Published: March 30, 2023

Special AT-rich sequence binding protein 1 (SATB1) has long been proposed to act as a global chromatin loop organizer in T cells. However, the exact functions of SATB1 spatial genome organization remain elusive. Here we show that depletion human and murine cells leads transcriptional dysregulation for genes involved cell activation, well alterations 3D architecture at multiple levels, including compartments, topologically associating domains, loops. Importantly, extensively colocalizes with CTCF throughout genome. Depletion increased contacts among across SATB1/CTCF co-occupied sites, thereby affecting transcription critical regulators activation. The loss does not affect occupancy but significantly reduces retention nuclear matrix. Collectively, our data contributes by constraining topology surrounding CTCF-binding sites.

Language: Английский

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Effect of loops on the mean-square displacement of Rouse-model chromatin

Physical review. E, Journal Year: 2024, Volume and Issue: 109(4)

Published: April 9, 2024

Chromatin polymer dynamics are commonly described using the classical Rouse model. The subsequent discovery, however, of intermediate-scale chromatin organization known as topologically associating domains (TADs) in experimental Hi-C contact maps for chromosomes across tree life, together with success loop extrusion factor (LEF) model explaining TAD formation, motivates efforts to understand effect loops and on dynamics. This paper seeks fulfill this need by combining LEF-model simulations extended Rouse-model investigate dynamic extrusion. We show that significantly suppress averaged mean-square displacement (MSD) a gene locus, consistent recent experiments track fluorescently labeled loci. also find reduce MSD's stretching exponent from value 1/2 loop-density-dependent 0.45--0.40 range. Remarkably, values range have been observed [Weber et al., Phys. Rev. Lett. 104, 238102 (2010); Bailey Mol. Biol. Cell 34, ar78 (2023)]. itself negligibly affects mobility. By studying static ``rosette'' configurations, we demonstrate MSDs exponents depend location locus question relative position local friction environment.

Language: Английский

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A dynamic role for transcription factors in restoring transcription through mitosis

Biochemical Society Transactions, Journal Year: 2024, Volume and Issue: 52(2), P. 821 - 830

Published: March 25, 2024

Mitosis involves intricate steps, such as DNA condensation, nuclear membrane disassembly, and phosphorylation cascades that temporarily halt gene transcription. Despite this disruption, daughter cells remarkably retain the parent cell's expression pattern, allowing for efficient transcriptional memory after division. Early studies in mammalian suggested transcription factors (TFs) mark genes swift reactivation, a phenomenon termed ‘mitotic bookmarking’, but conflicting data emerged regarding TF presence on mitotic chromosomes. Recent advancements live-cell imaging fixation-free genomics challenge conventional belief universal formaldehyde fixation, revealing dynamic interactions during mitosis. Here, we review recent provide examples of at least four modes TF–DNA interaction mitosis molecular mechanisms govern these interactions. Additionally, explore impact initiation post-mitosis. Taken together, call paradigm shift toward model behavior mitosis, underscoring need incorporating dynamics mechanistic models re-establishing

Language: Английский

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