Rearrangement of 3D genome organization in breast cancer epithelial - mesenchymal transition and metastasis organotropism DOI Open Access
Priyojit Das, Rebeca San Martin, Tian Hong

и другие.

Опубликована: Дек. 23, 2024

Breast cancer cells exhibit organotropism during metastasis, showing preferential homing to certain organs such as bone, lung, liver, and brain. One potential explanation for this organotropic behavior is that gain properties enable thriving in microenvironments. Such specific metastatic traits may arise from gene regulation at the primary tumor site. Spatial genome organization plays a crucial role oncogenic transformation progression, but extent which chromosome architecture contributes organ-specific unclear. This work characterizes changes associated with traits. By comparing collection of genomic data different subtypes localized lung breast both normal cancerous cells, we find important trends reorganization. The most striking differences 3D compartments segregate cell types according their epithelial vs. mesenchymal status. EMT compartment signature occurs regions distinct transcription-defined signatures, suggesting separate layer regulation. Specifically querying organotropism, consistent adaptations needed survive new microenvironment, exhibiting switch signatures shift cell-like conformation brain prostate shifts toward brain-like state. TCGA patient reveals expression concordant these organ-permissive changes. These results suggest provides an additional level fate specification informing enabling survival

Язык: Английский

p63: A Master Regulator at the Crossroads Between Development, Senescence, Aging, and Cancer DOI Creative Commons
Lakshana Sruthi Sadu Murari,

S Kunkel,

Anala V. Shetty

и другие.

Cells, Год журнала: 2025, Номер 14(1), С. 43 - 43

Опубликована: Янв. 3, 2025

The p63 protein is a master regulatory transcription factor that plays crucial roles in cell differentiation, adult tissue homeostasis, and chromatin remodeling, its dysregulation associated with genetic disorders, physiological premature aging, cancer. effects of are carried out by two main isoforms regulate proliferation senescence. also controls the epigenome regulating interactions histone modulators, such as acetyltransferase p300, deacetylase HDAC1/2, DNA methyltransferases. miRNA-p63 critical regulators context cancer metastasis. This review aims to elaborate on diverse p63, focusing disease, development, mechanisms controlling genome organization function.

Язык: Английский

Процитировано

0
Bridging scales in chromatin organization: Computational models of loop formation and their implications for genome function DOI
Shingo Tsukamoto, Mohammad R. K. Mofrad

The Journal of Chemical Physics, Год журнала: 2025, Номер 162(5)

Опубликована: Фев. 7, 2025

Chromatin loop formation plays a crucial role in 3D genome interactions, with misfolding potentially leading to irregular gene expression and various diseases. While experimental tools such as Hi-C have advanced our understanding of the biophysical principles underlying chromatin remain elusive. This review examines computational approaches folding, focusing on polymer models that elucidate mechanics. We discuss three key models: (1) multi-loop-subcompartment model, which investigates structural effects loops conformation; (2) strings binders switch capturing thermodynamic aggregation; (3) extrusion revealing maintenance chromosome complexes. In addition, we explore address clustering heterogeneity biological processes disease progression. The concludes an outlook open questions current trends emphasizing physical challenges field.

Язык: Английский

Процитировано

0
Deciphering Pre-existing and Induced 3D Genome Architecture Changes involved in Constricted Melanoma Migration DOI Creative Commons
Christopher Playter, Rosela Golloshi,

Joshua H. Garretson

и другие.

iScience, Год журнала: 2025, Номер unknown, С. 112346 - 112346

Опубликована: Апрель 1, 2025

Metastatic cancer cells traverse constricted spaces that exert forces on their nucleus and the genomic contents within. Cancerous tumors are highly heterogeneous not all within them can achieve such a feat. Here, we investigated what initial genome architecture characteristics favor migratory ability of which arise only after passage through multiple constrictions. We identified cell surface protein (ITGB4) whose expression correlates with increased migration in human melanoma A375 cells. Sorting out this subpopulation allowed us to identify cellular nuclear features pre-exist migration, as well alterations appear have passed specific regions experienced altered spatial compartment profiles migration. Our study reveals 3D structure contributions both selection induction mechanisms fate change during metastasis.

Язык: Английский

Процитировано

0
Uncovering Changes in 3D‐Chromatin Structure and Dynamic Gene Expression During Spermatogenesis DOI

H. Jin,

Yuan Ma,

Yaru Xie

и другие.

The FASEB Journal, Год журнала: 2025, Номер 39(7)

Опубликована: Апрель 8, 2025

ABSTRACT Spermatogonial stem cells (SSCs) have the potential for self‐renewal and differentiation, normal spermatogenesis maintains a stable number of spermatogonial spermatozoa. Spermatogenesis is accompanied by changes in three‐dimensional structure chromatin gene expression, but structural differences between stages higher‐order dynamics not yet been elucidated. Consequently, we conducted high‐throughput analysis organization expression using porcine spermatogonia (SPG), spermatocytes (SPY) round spermatids (RS). We found that during spermatogenesis, SPY showed weaker pattern chromosomal interactions, attenuated compartmentalisation, reduction TADs (topological associating domains), which was restored subsequent period spermatids. These findings suggest reprogramming structures differentiation. Our results reveal along with expression. In conclusion, our study reveals interrelationships spermatogonia, spermatocytes, spermatids, providing new insights into understanding as well basic theoretical data male reproductive techniques biological sciences.

Язык: Английский

Процитировано

0
3D genome folding in epigenetic regulation and cellular memory DOI Creative Commons
Flora Paldi, Giacomo Cavalli

Trends in Cell Biology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

The 3D folding of the genome is tightly linked to its epigenetic state which maintains gene expression programmes. Although relationship between and organisation highly context dependent, emerging as a novel layer reinforce stabilise transcriptional states. Whether regulatory information carried in could be transmitted through mitosis an area active investigation. In this review, we discuss nuclear organisation, well interplay regulation folding. We also consider architectural remodelling nuclei cells enter exit mitosis, evaluate potential contribute cellular memory.

Язык: Английский

Процитировано

0
Polymer model integrates imaging and sequencing to reveal how nanoscale heterochromatin domains influence gene expression DOI Creative Commons

Vinayak Vinayak,

Ramin Basir, Rosela Golloshi

и другие.

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

Опубликована: Апрель 23, 2025

Abstract Chromatin organization regulates gene expression, with nanoscale heterochromatin domains playing a fundamental role. Their size varies microenvironmental stiffness and epigenetic interventions, but how these factors regulate their formation influence transcription remains unclear. To address this, we developed sequencing-informed copolymer model that simulates chromatin evolution through diffusion active reactions. Our predicts the of quantifies domain scales reaction rates, showing compaction changes primarily occur at boundaries. We validated predictions via Hi-C super-resolution imaging hyperacetylated melanoma cells identified differential expression metastasis-related genes RNA-seq. our findings in hMSCs, where rates respond to stiffness. Conclusively, simulations reveal boundaries memory. These demonstrate external cues drive transcriptional memory development disease.

Язык: Английский

Процитировано

0
HIRA-dependent provision of histone H3.3 in active chromatin ensures genome compartmentalisation DOI Open Access
Tina Karagyozova, Alberto Gatto, Audrey Forest

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 28, 2024

The mammalian genome, organised into chromatin, adopts a three-dimensional (3D) folding within the cell nucleus with spatially segregated active and repressed compartments, termed A B. However, how nucleosome deposition impacts these levels of organisation is unknown. Here, we monitored changes in 3D genome by Hi-C after impairing chaperone HIRA, involved histone H3.3 deposition. In absence enrichment decreases compartment that also shows weaker interactions. At this scale, post-translational modifications (PTMs) do not follow changes. line impaired maintenance, accessibility measured ATAC-seq increases. Specifically, at genes, increases gene bodies but promoters where compensation H3.1 reduces turnover. Notably, regions flanking genes show reduced insulation. We conclude HIRA-dependent pathway key to maintain higher order impact compartmentalisation independently PTMs.

Язык: Английский

Процитировано

2
Deciphering Pre-existing and Induced 3D Genome Architecture Changes involved in Constricted Melanoma Migration DOI Open Access
Christopher Playter, Rosela Golloshi,

Joshua H. Garretson

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 22, 2024

Metastatic cancer cells traverse constricted spaces that exert forces on their nucleus and the genomic contents within. Cancerous tumors are highly heterogeneous not all within them can achieve such a feat. Here, we investigated what initial genome architecture characteristics favor migratory ability of which arise only after passage through multiple constrictions. We identified cell surface protein (ITGB4) whose expression correlates with increased migration in human melanoma A375 cells. Sorting out this subpopulation allowed us to identify cellular nuclear features pre-exist migration, as well alterations appear have passed specific regions experienced altered spatial compartment profiles migration. Our study reveals 3D structure contributions both selection induction mechanisms fate change during metastasis.

Язык: Английский

Процитировано

0
Rethinking Models of DNA Organization in Micrometer‐Sized Chromosomes from the Perspective of the Nanoproperties of Chromatin Favoring a Multilayer Structure DOI Creative Commons
Joan‐Ramon Daban

Small Structures, Год журнала: 2024, Номер 5(10)

Опубликована: Сен. 4, 2024

The long genomic DNA molecules in eukaryotes are fragile and prone to entanglement, must be tightly folded fit into the micrometric dimensions of mitotic chromosomes. Histones transform monotonous linear structure double‐helical a chromatin filament formed by many nucleosomes. A physically consistent model for packaging compatible with all constraints imposed structural properties It has 1) high concentration elongated cylindrical shape chromosomes 2) known self‐associative chromatin, also 3) an effective protection chromosomal from topological entanglement mechanical breakage. multilayer chromosome model, which repetitive weak interaction between nucleosomes at nanoscale produces stacking layers, is these constraints. self‐organization whole current knowledge self‐assembly structures different building blocks. justifies geometry bands translocations, feasible physical mechanisms control gene expression, replication, repair, segregation daughter cells.

Язык: Английский

Процитировано

0
Polymer Model Integrates Super-Resolution Imaging and Epigenomic Sequencing to Elucidate the Role of Epigenetic Reactions in Shaping 4D Chromatin Organization DOI Open Access

Vinayak Vinayak,

Ramin Basir, Rosela Golloshi

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 12, 2024

Abstract Chromatin, with its complex spatial and temporal organization, plays a crucial role in regulating gene expression. Recent advancements super-resolution microscopy have revealed that nanoscale domains of heterochromatin (repressed segments) embedded within euchromatin (active background are fundamental units 3D chromatin organization. In tissue-resident cells, the size these varies microenvironment, particularly stiffness, organization is also influenced by pharmacological epigenetic drugs. However, mechanisms governing domain under various conditions their impact on expression remain unclear. To address this knowledge gap, we developed dynamic, next-generation sequencing informed copolymer model. Our model simulates spatiotemporal evolution chromatin, driven passive diffusion active reactions, which interconvert heterochromatin. By integrating chromatin-chromatin interaction energetics diffusion-reaction dynamics, predict formation heterochromatin-rich establish scaling relationship between modulation reaction rates. Additionally, our predicts compaction changes response to global rates occur predominantly at boundaries. We validated predictions via Hi-C contact map analysis imaging hyperacetylated melanoma cells. Subsequent RNA-seq suggested pivotal shifts influencing metastatic potential further mesoscale findings against rearrangement hMSCs, exhibit sensitivity microenvironmental stiffness. Finally, evaluated effects cycling silico, mimicking cellular transition different extracellular conditions, back again. This finding reveals cell-type invariant mechanism boundaries, whereby guides memory formation. show reorganization resulting from alterations drug exposure disease progression impacts both immediate responses long-term memory.

Язык: Английский

Процитировано

0