Ontology highlight
ABSTRACT:
PROVIDER: PRJNA853734 | ENA |
REPOSITORIES: ENA
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Project description:Chromatin architecture is a fundamental mediator of genome function. Fasting is a major environmental cue across the animal kingdom. Yet, how it impacts on 3D genome organization is unknown. Here, we show that fasting induces an intestine-specific, reversible, and large-scale spatial reorganization of chromatin in C. elegans. This fasting-induced 3D genome reorganization requires inhibition of the nutrient-sensing mTOR pathway, through the regulation of RNA Pol I, but not Pol II nor Pol III, and is accompanied by remodeling of the nucleolus. By uncoupling the 3D genome configuration from the animal´s nutritional status we find that the spatial reorganization of chromatin correlates with the expression of metabolic and stress-related genes, potentially supporting the transcriptional response in fasted animals. Our work documents the first large-scale chromatin reorganization triggered by fasting and reveals that mTOR and RNA Pol I shape genome architecture in response to nutrients.
2024-07-19 | GSE268926 | GEO
Project description:Chromatin architecture is a fundamental mediator of genome function. Fasting is a major environmental cue across the animal kingdom. Yet, how it impacts on 3D genome organization is unknown. Here, we show that fasting induces an intestine-specific, reversible, and large-scale spatial reorganization of chromatin in C. elegans. This fasting-induced 3D genome reorganization requires inhibition of the nutrient-sensing mTOR pathway, through the regulation of RNA Pol I, but not Pol II nor Pol III, and is accompanied by remodeling of the nucleolus. By uncoupling the 3D genome configuration from the animal´s nutritional status we find that the spatial reorganization of chromatin correlates with the expression of metabolic and stress-related genes, potentially supporting the transcriptional response in fasted animals. Our work documents the first large-scale chromatin reorganization triggered by fasting and reveals that mTOR and RNA Pol I shape genome architecture in response to nutrients.
2024-07-19 | GSE268974 | GEO
Project description:We analyzed the impact of NSD2 overexpression on 3D genome reorganization and gene expression in multiple myeloma cell lines
2019-09-03 | GSE131651 | GEO
Project description:β3-adrenergic receptor (β3-AR) hormonal signaling is imperative for adaptative thermogenesis, facilitating heat generation during cold exposure. This study explores how β3-AR signaling regulates thermogenic gene activation by altering the three-dimensional (3D) genome organization. Our findings reveal a rapid 3D genome reorganization in brown adipocytes following 4 hours of β3-AR stimulation, highlighted by high-resolution Micro-C analysis. This reorganization involves substantial dynamic changes in chromatin loops, coupled with activation of genes involved in thermogenesis. Mechanistically, β3-AR signaling promotes the p18Hamlet/SRCAP complex assembly, catalyzing the chromatin incorporation of the histone variant H2A.Z. H2A.Z incorporation enhances chromatin accessibility at loop anchors, facilitating loop formation. Disruption of H2A.Z impairs loop dynamics and thermogenic function of brown adipocytes, with implications for both mice and humans. Notably, human homologous loop anchors are associated with obesity-related genetic variants. This study underscores the critical role of 3D genome architecture in thermogenic regulation, offering new dimensions into obesity’s molecular underpinnings.
2026-02-17 | GSE261412 | GEO
Project description:β3-adrenergic receptor (β3-AR) hormonal signaling is imperative for adaptative thermogenesis, facilitating heat generation during cold exposure. This study explores how β3-AR signaling regulates thermogenic gene activation by altering the three-dimensional (3D) genome organization. Our findings reveal a rapid 3D genome reorganization in brown adipocytes following 4 hours of β3-AR stimulation, highlighted by high-resolution Micro-C analysis. This reorganization involves substantial dynamic changes in chromatin loops, coupled with activation of genes involved in thermogenesis. Mechanistically, β3-AR signaling promotes the p18Hamlet/SRCAP complex assembly, catalyzing the chromatin incorporation of the histone variant H2A.Z. H2A.Z incorporation enhances chromatin accessibility at loop anchors, facilitating loop formation. Disruption of H2A.Z impairs loop dynamics and thermogenic function of brown adipocytes, with implications for both mice and humans. Notably, human homologous loop anchors are associated with obesity-related genetic variants. This study underscores the critical role of 3D genome architecture in thermogenic regulation, offering new dimensions into obesity’s molecular underpinnings.
2026-02-17 | GSE261410 | GEO
Project description:Spatiotemporal regulation of chromatin replication (replication timing, RT） in eukaryotes is critical to maintain the genomic integrity. Here we focused on epigenetic mechanisms in rewiring genomic 3D conformation and replication timing. The results show that the novel lysine β-hydroxybutyrylation (Kbhb) modifications accelerates chromatin replication without inducing replication defects. This effect was mediated by the NAT10, a novel b-hydroxybutyryl-transferase, through regulating the association of NAT10 and CTCF with chromatin. Depletion of NAT10 and NAT10-mediated Kbhb dramatically reduce chromatin-bound NAT10 and CTCF, resulting in reorganization of genomic 3D conformation with enhanced trans- and cis-interaction in Hi-C matrix, with elevated proportion of A compartments, and with reorganized TADs boundaries. Moreover, reorganization of genomic 3D conformation contributes to rewire replication timing. These results support models in which NAT10-mediated β-hydroxybutyrylation coordinates genomic 3D conformation reorganization with replication timing alteration, and emphatically address the concept that epigenetic mechanisms reconcile genomic 3D conformation with replication timing.
2021-09-08 | GSE175731 | GEO
Project description:While it is well-established that UV radiation threatens genomic integrity, the precise mechanisms by which cells orchestrate DNA damage response and repair within the context of 3D genome architecture remain unclear. Here, we address this gap by investigating the UV-induced reorganization of the 3D genome and its critical role in mediating damage response. Employing temporal maps of contact matrices and transcriptional profiles, we illustrate the immediate and holistic changes in genome architecture post-irradiation, emphasizing the significance of this reconfiguration for effective DNA repair processes. We demonstrate that UV radiation triggers a comprehensive restructuring of the 3D genome structure at all levels, including loops, topologically associating domains and compartments. Through the analysis of DNA damage and excision repair maps, we uncover a correlation between genome folding, gene regulation, damage formation probability, and repair efficacy. We show that adaptive reorganization of the 3D genome is a key mediator of the damage response, providing new insights into the complex interplay of genomic structure and cellular defense mechanisms against UV-induced damage, thereby advancing our understanding of cellular resilience.
2024-05-27 | GSE268349 | GEO
Project description:While it is well-established that UV radiation threatens genomic integrity, the precise mechanisms by which cells orchestrate DNA damage response and repair within the context of 3D genome architecture remain unclear. Here, we address this gap by investigating the UV-induced reorganization of the 3D genome and its critical role in mediating damage response. Employing temporal maps of contact matrices and transcriptional profiles, we illustrate the immediate and holistic changes in genome architecture post-irradiation, emphasizing the significance of this reconfiguration for effective DNA repair processes. We demonstrate that UV radiation triggers a comprehensive restructuring of the 3D genome structure at all levels, including loops, topologically associating domains and compartments. Through the analysis of DNA damage and excision repair maps, we uncover a correlation between genome folding, gene regulation, damage formation probability, and repair efficacy. We show that adaptive reorganization of the 3D genome is a key mediator of the damage response, providing new insights into the complex interplay of genomic structure and cellular defense mechanisms against UV-induced damage, thereby advancing our understanding of cellular resilience.
2024-05-27 | GSE268350 | GEO
Project description:The goals of this study are to determine whether alterations in the 3D genome organization are associated with the malignant transformation of T-ALL. We report integrated analyses of 3D genome alterations and differentially expressed genes (DEGs) in 18 newly diagnosed T-ALL patients and 4 healthy T cell controls. We found that 3D genome reorganization at the compartment, topologically associated domains (TAD), and loop levels in different subtypes of T-ALL. Alterations in the 3D genome were associated with nearly 45% of the upregulated genes in T-ALL. We also identified 34 novel translocations in the noncoding regions of the genome and 44 new loops formed between translocated chromosomes. These translocations can activate the expression of oncogenic transcription factors including HOXA11-A13 by “cis” or “trans” reorganization of chromatin structure. Our analysis demonstrated that T-ALLs with HOXA cluster overexpression were heterogeneous clinical entities, and ectopic expressions of the HOXA11-A13 genes, but not other genes in the HOXA cluster, were associated with immature phenotypes and poor outcomes. Our findings highlight the potentially important roles of 3D genome alterations in the etiology and prognosis of T-ALL.
2021-03-20 | GSE146901 | GEO
Project description:Despite recent advances, the dynamics of genome architecture and chromatin function during human cell differentiation and its potential reorganization upon neoplastic transformation remains poorly characterized. Here, we integrate in situ Hi-C and nine additional omic layers to define and biologically characterize the dynamic changes in three-dimensional (3D) genome architecture across normal B cell differentiation and in neoplastic cells from different subtypes of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) patients. Beyond conventional active (A) and inactive (B) compartments, an integrative analysis of Hi-C data uncovers a highly-dynamic intermediate compartment enriched in poised and polycomb-repressed chromatin. During B cell development, we detect that 28% of the compartments change at defined maturation stages and mostly involve the intermediate compartment. The transition from naive to germinal center B cells is associated with widespread chromatin activation, which mostly reverts into the naive state upon further maturation of germinal center cells into memory B cells. The analysis of CLL and MCL neoplastic cells points both to entity and subtype-specific alterations in chromosome organization. Remarkably, we observe that large chromatin blocks containing key disease-specific genes alter their 3D genome organization. These include the inactivation of a 2Mb region containing the EBF1 gene in CLL and the activation of a 6.1Mb region containing the SOX11 gene in clinically aggressive MCL. This study indicates that 3D genome interactions are extensively modulated during normal B cell differentiation and that the genome of B cell neoplasias acquires a tumor-specific 3D genome architecture.
| EGAS00001004763 | EGA