Effect of fasting on transcription in intestinal cells dissected from adult C. elegans
Ontology highlight
ABSTRACT: 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.
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.
Project description:Understanding the topological configurations of chromatin can reveal valuable insights into how the genome and epigenome act in concert to control cell fate during development. Here we generate high-resolution architecture maps across seven genomic loci in embryonic stem cells and neural progenitor cells. We observe a hierarchy of 3-D interactions that undergo marked reorganization at the sub-Mb scale during differentiation. Distinct combinations of CTCF, Mediator, and cohesin show widespread enrichment in architecture at different length scales. CTCF/cohesin anchor long-range constitutive interactions that might form the topological basis for invariant sub-domains. Conversely, Mediator/cohesin together with pioneer factors bridge short-range enhancer-promoter interactions within and between larger sub-domains. Knockdown of Smc1 or Med12 in ES cells results in disruption of spatial architecture and down-regulation of genes found in cohesin-mediated interactions. We conclude that cell type-specific chromatin organization occurs at the sub-Mb scale and that architectural proteins shape the genome in hierarchical length scales. Analysis of higher-order chromatin chromatin architecture in mouse ES cells and ES-derived NPCs. Analysis of CTCF and Smc1 occupied sites in ES-derived NPCs.
Project description:The emerging 4D genome project aiming to map the dynamics of genomes in spatial and temporal dimension has put forward to developing the mechanisms of how the nucleus is organized and functions. Therefore, processes like cellular senescence characterized by complex events give rise to understanding the regulation network from 1D genome to dynamically organized 3D structure. Unfortunately, how spatial genome reorganization triggers cellular senescence and how it influences senescence-related downstream transcriptional profile remains unaddressed well. Here, we uncover that re re-orchestration of 3D chromatin architecture has occurred in cellular senescence, accompanied with remodeling of enhancer repertories, which in turn facilicate the recruitment of the chromatin reader C/EBPα to newly activated senescence enhancers (SAEs), leading to the expression of SAEs flanking SASP genes kinetics.
Project description:The emerging 4D genome project aiming to map the dynamics of genomes in spatial and temporal dimension has put forward to developing the mechanisms of how the nucleus is organized and functions. Therefore, processes like cellular senescence characterized by complex events give rise to understanding the regulation network from 1D genome to dynamically organized 3D structure. Unfortunately, how spatial genome reorganization triggers cellular senescence and how it influences senescence-related downstream transcriptional profile remains unaddressed well. Here, we uncover that re re-orchestration of 3D chromatin architecture has occurred in cellular senescence, accompanied with remodeling of enhancer repertories, which in turn facilicate the recruitment of the chromatin reader C/EBPα to newly activated senescence enhancers (SAEs), leading to the expression of SAEs flanking SASP genes kinetics.
Project description:The emerging 4D genome project aiming to map the dynamics of genomes in spatial and temporal dimension has put forward to developing the mechanisms of how the nucleus is organized and functions. Therefore, processes like cellular senescence characterized by complex events give rise to understanding the regulation network from 1D genome to dynamically organized 3D structure. Unfortunately, how spatial genome reorganization triggers cellular senescence and how it influences senescence-related downstream transcriptional profile remains unaddressed well. Here, we uncover that re re-orchestration of 3D chromatin architecture has occurred in cellular senescence, accompanied with remodeling of enhancer repertories, which in turn facilicate the recruitment of the chromatin reader C/EBPα to newly activated senescence enhancers (SAEs), leading to the expression of SAEs flanking SASP genes kinetics.
Project description:Understanding the topological configurations of chromatin can reveal valuable insights into how the genome and epigenome act in concert to control cell fate during development. Here we generate high-resolution architecture maps across seven genomic loci in embryonic stem cells and neural progenitor cells. We observe a hierarchy of 3-D interactions that undergo marked reorganization at the sub-Mb scale during differentiation. Distinct combinations of CTCF, Mediator, and cohesin show widespread enrichment in architecture at different length scales. CTCF/cohesin anchor long-range constitutive interactions that might form the topological basis for invariant sub-domains. Conversely, Mediator/cohesin together with pioneer factors bridge short-range enhancer-promoter interactions within and between larger sub-domains. Knockdown of Smc1 or Med12 in ES cells results in disruption of spatial architecture and down-regulation of genes found in cohesin-mediated interactions. We conclude that cell type-specific chromatin organization occurs at the sub-Mb scale and that architectural proteins shape the genome in hierarchical length scales.
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.
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.