Ribosome biogenesis disruption mediated chromatin structure changes in C. elegans larvae revealed by SRAtac, an integrated, customizable end to end analysis pipeline for ATAC-seq
Ontology highlight
ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE218280 | GEO | 2022/11/29
REPOSITORIES: GEO
Similar Datasets
Project description:Nucleolus is the organelle for ribosome biogenesis and sensing various types of stress. Its role in regulating stem cell fate is unclear. Here, we present multiple lines of evidence that nucleolar stress induced by interfering rRNA biogenesis can drive two-cell stage embryo-like (2C-like) transcriptional program and induce an expanded 2C-like cell population in mouse embryonic stem (mES) cells. Mechanistically, the liquid-liquid phase separation (LLPS) mediated by rRNA and nucleolar proteins maintains the formation of peri-nucleolar heterochromatin (PNH). When mES cells undergo rRNA biogenesis defect, the normal LLPS of nucleolus is disrupted, causing deconjugation of NCL/TRIM28 complex on PNH and changes of epigenetic state and 3D structure of PNH, which leads to Dux, a conserved multicopy retrogene defining the cleavage-specific transcriptional program in placental mammals, to be released from the PNH region, activation of 2C-like program and transition of mES cells to 2C-like cells. Embryos with rRNA biogenesis defect are incompatible to develop from 2-cell (2C) to blastocyte (BC) and appear to skew from the blastocyst to earlier cleavage embryo signatures. Our results highlight that nucleolar LLPS-mediated 3D chromatin structure reshaping of PNH compartment regulates the fate transition of mES cells to 2C-like cells. Our findings for the first time elucidate the novel roles of rRNA biogenesis in regulating the 2C-like and ES state homeostasis in cultured cells and suggest that rRNA biogenesis is a new molecular switch from nucleolus-unmatured 2C stage to nucleolus-matured BC stage during murine pre-implantation embryo development.
2021-09-15 | GSE166032 | GEO
Project description:Nucleolus is the organelle for ribosome biogenesis and sensing various types of stress. Its role in regulating stem cell fate is unclear. Here, we present multiple lines of evidence that nucleolar stress induced by interfering rRNA biogenesis can drive two-cell stage embryo-like (2C-like) transcriptional program and induce an expanded 2C-like cell population in mouse embryonic stem (mES) cells. Mechanistically, the liquid-liquid phase separation (LLPS) mediated by rRNA and nucleolar proteins maintains the formation of peri-nucleolar heterochromatin (PNH). When mES cells undergo rRNA biogenesis defect, the normal LLPS of nucleolus is disrupted, causing deconjugation of NCL/TRIM28 complex on PNH and changes of epigenetic state and 3D structure of PNH, which leads to Dux, a conserved multicopy retrogene defining the cleavage-specific transcriptional program in placental mammals, to be released from the PNH region, activation of 2C-like program and transition of mES cells to 2C-like cells. Embryos with rRNA biogenesis defect are incompatible to develop from 2-cell (2C) to blastocyte (BC) and appear to skew from the blastocyst to earlier cleavage embryo signatures. Our results highlight that nucleolar LLPS-mediated 3D chromatin structure reshaping of PNH compartment regulates the fate transition of mES cells to 2C-like cells. Our findings for the first time elucidate the novel roles of rRNA biogenesis in regulating the 2C-like and ES state homeostasis in cultured cells and suggest that rRNA biogenesis is a new molecular switch from nucleolus-unmatured 2C stage to nucleolus-matured BC stage during murine pre-implantation embryo development.
2021-09-15 | GSE166023 | GEO
Project description:Nucleolus is the organelle for ribosome biogenesis and sensing various types of stress. Its role in regulating stem cell fate is unclear. Here, we present multiple lines of evidence that nucleolar stress induced by interfering rRNA biogenesis can drive two-cell stage embryo-like (2C-like) transcriptional program and induce an expanded 2C-like cell population in mouse embryonic stem (mES) cells. Mechanistically, the liquid-liquid phase separation (LLPS) mediated by rRNA and nucleolar proteins maintains the formation of peri-nucleolar heterochromatin (PNH). When mES cells undergo rRNA biogenesis defect, the normal LLPS of nucleolus is disrupted, causing deconjugation of NCL/TRIM28 complex on PNH and changes of epigenetic state and 3D structure of PNH, which leads to Dux, a conserved multicopy retrogene defining the cleavage-specific transcriptional program in placental mammals, to be released from the PNH region, activation of 2C-like program and transition of mES cells to 2C-like cells. Embryos with rRNA biogenesis defect are incompatible to develop from 2-cell (2C) to blastocyte (BC) and appear to skew from the blastocyst to earlier cleavage embryo signatures. Our results highlight that nucleolar LLPS-mediated 3D chromatin structure reshaping of PNH compartment regulates the fate transition of mES cells to 2C-like cells. Our findings for the first time elucidate the novel roles of rRNA biogenesis in regulating the 2C-like and ES state homeostasis in cultured cells and suggest that rRNA biogenesis is a new molecular switch from nucleolus-unmatured 2C stage to nucleolus-matured BC stage during murine pre-implantation embryo development.
2021-09-15 | GSE166027 | GEO
Project description:Nucleolus is the organelle for ribosome biogenesis and sensing various types of stress. Its role in regulating stem cell fate is unclear. Here, we present multiple lines of evidence that nucleolar stress induced by interfering rRNA biogenesis can drive two-cell stage embryo-like (2C-like) transcriptional program and induce an expanded 2C-like cell population in mouse embryonic stem (mES) cells. Mechanistically, the liquid-liquid phase separation (LLPS) mediated by rRNA and nucleolar proteins maintains the formation of peri-nucleolar heterochromatin (PNH). When mES cells undergo rRNA biogenesis defect, the normal LLPS of nucleolus is disrupted, causing deconjugation of NCL/TRIM28 complex on PNH and changes of epigenetic state and 3D structure of PNH, which leads to Dux, a conserved multicopy retrogene defining the cleavage-specific transcriptional program in placental mammals, to be released from the PNH region, activation of 2C-like program and transition of mES cells to 2C-like cells. Embryos with rRNA biogenesis defect are incompatible to develop from 2-cell (2C) to blastocyte (BC) and appear to skew from the blastocyst to earlier cleavage embryo signatures. Our results highlight that nucleolar LLPS-mediated 3D chromatin structure reshaping of PNH compartment regulates the fate transition of mES cells to 2C-like cells. Our findings for the first time elucidate the novel roles of rRNA biogenesis in regulating the 2C-like and ES state homeostasis in cultured cells and suggest that rRNA biogenesis is a new molecular switch from nucleolus-unmatured 2C stage to nucleolus-matured BC stage during murine pre-implantation embryo development.
2021-09-15 | GSE166025 | GEO
Project description:Nucleolus is the organelle for ribosome biogenesis and sensing various types of stress. Its role in regulating stem cell fate is unclear. Here, we present multiple lines of evidence that nucleolar stress induced by interfering rRNA biogenesis can drive two-cell stage embryo-like (2C-like) transcriptional program and induce an expanded 2C-like cell population in mouse embryonic stem (mES) cells. Mechanistically, the liquid-liquid phase separation (LLPS) mediated by rRNA and nucleolar proteins maintains the formation of peri-nucleolar heterochromatin (PNH). When mES cells undergo rRNA biogenesis defect, the normal LLPS of nucleolus is disrupted, causing deconjugation of NCL/TRIM28 complex on PNH and changes of epigenetic state and 3D structure of PNH, which leads to Dux, a conserved multicopy retrogene defining the cleavage-specific transcriptional program in placental mammals, to be released from the PNH region, activation of 2C-like program and transition of mES cells to 2C-like cells. Embryos with rRNA biogenesis defect are incompatible to develop from 2-cell (2C) to blastocyte (BC) and appear to skew from the blastocyst to earlier cleavage embryo signatures. Our results highlight that nucleolar LLPS-mediated 3D chromatin structure reshaping of PNH compartment regulates the fate transition of mES cells to 2C-like cells. Our findings for the first time elucidate the novel roles of rRNA biogenesis in regulating the 2C-like and ES state homeostasis in cultured cells and suggest that rRNA biogenesis is a new molecular switch from nucleolus-unmatured 2C stage to nucleolus-matured BC stage during murine pre-implantation embryo development.
2021-09-15 | GSE166022 | GEO
Project description:The nucleolus is a membraneless organelle responsible for ribosome biogenesis, perinuclear heterochromatin formation, and genome stability regulation. However, how cell fate decision occurs, including early embryonic development, ESC differentiation, and tumorigenesis, remains poorly understood at the nucleolar level. It has been observed that large nucleoli and rDNA hyperactivity are common in pluripotent stem cells and tumor cells, while the nucleolus shrinks and rDNA transcriptional activity decrease during lineage commitment. iPSCs nucleolar size and rDNA transcriptional activity are greater than that before reprogramming. It remains unclear how and when the differentiated cell nucleoli convert to the stem cell nucleoli during iPSC reprogramming.In this study, we found that nucleolar remodeling, manifested as enlarged nucleolus, activation of rDNA transcription, enhanced activity of nucleolar organizing regions (NORs), and conversion of reticular nucleolar ultrastructure into low-granular, is an early and stage-specific event that occurs during iPSCs reprogramming. Our study highlights the importance of rDNA transcriptional activity in the early stages of iPSC reprogramming, which is crucial for nucleolar remodeling and regaining stemness. Interfering rDNA transcription hinders nucleolar remodeling, which has disastrous consequences for chromatin remodeling in early stage of iPSC reprogramming and iPSCs establishment. Moreover, our results revealed a nucleolar regulation on chromatin accessibility during iPSC reprogramming and identified some candidate genes (Mybl2, Bard1 and other chromosome related genes) that might be associated with iPSC reprogramming, which may apply to nucleolar remodeling in other cell fated decision.
2024-10-01 | GSE232871 | GEO
Project description:The nucleolus is a membraneless organelle responsible for ribosome biogenesis, perinuclear heterochromatin formation, and genome stability regulation. However, how cell fate decision occurs, including early embryonic development, ESC differentiation, and tumorigenesis, remains poorly understood at the nucleolar level. It has been observed that large nucleoli and rDNA hyperactivity are common in pluripotent stem cells and tumor cells, while the nucleolus shrinks and rDNA transcriptional activity decrease during lineage commitment. iPSCs nucleolar size and rDNA transcriptional activity are greater than that before reprogramming. It remains unclear how and when the differentiated cell nucleoli convert to the stem cell nucleoli during iPSC reprogramming.In this study, we found that nucleolar remodeling, manifested as enlarged nucleolus, activation of rDNA transcription, enhanced activity of nucleolar organizing regions (NORs), and conversion of reticular nucleolar ultrastructure into low-granular, is an early and stage-specific event that occurs during iPSCs reprogramming. Our study highlights the importance of rDNA transcriptional activity in the early stages of iPSC reprogramming, which is crucial for nucleolar remodeling and regaining stemness. Interfering rDNA transcription hinders nucleolar remodeling, which has disastrous consequences for chromatin remodeling in early stage of iPSC reprogramming and iPSCs establishment. Moreover, our results revealed a nucleolar regulation on chromatin accessibility during iPSC reprogramming and identified some candidate genes (Mybl2, Bard1 and other chromosome related genes) that might be associated with iPSC reprogramming, which may apply to nucleolar remodeling in other cell fated decision.
2024-10-01 | GSE232870 | GEO
Project description:The nucleolus composes hundreds of proteins that play distinct roles in ribosomal RNA (rRNA) processing within Fibrillar Center/Dense Fibrillar Component (FC/DFC) units and ribosome assembly in Granular Component (GC). The sub-nucleolar localization of most proteins and how their unique localization facilitates rRNA processing have remained elusive. By screening 200 nucleolar candidate proteins with high-resolution, live-cell microscopy, we identified a previously undescribed sub-nucleolar compartment, named the periphery of DFC (PDFC). Among the 12 proteins identified in PDFC, URB1 (unhealthy ribosome biogenesis 1) is required for PDFC organization and proper 3' end processing of 47S pre-rRNA. URB1 binds between the 28S rRNA and the 3' external transcribed spacer (3' ETS) to ensure 3' ETS removal, which occurs at the DFC/PDFC boundary. Loss of URB1 leads to accumulation of aberrant 3' ETS-retained 32S pre-rRNA variants, which activates exosome-dependent nucleolar surveillance. This causes decreased 28S rRNA production, reduced cell proliferation and retarded mouse embryonic pre-implementation development. Furthermore, urb1 depletion results in developmental craniofacial disorder in zebrafish, which can be at least partially rescued by further depleting exosome components. Together, this study provides new insights into functional sub-nucleolar organizations, identifies a physiologically essential step in rRNA maturation and emphasizes the exosome-dependent pre-rRNA surveillance pathway.
2023-01-04 | GSE194413 | GEO
Project description:The nucleolus composes hundreds of proteins that play distinct roles in ribosomal RNA (rRNA) processing within Fibrillar Center/Dense Fibrillar Component (FC/DFC) units and ribosome assembly in Granular Component (GC). The sub-nucleolar localization of most proteins and how their unique localization facilitates rRNA processing have remained elusive. By screening 200 nucleolar candidate proteins with high-resolution, live-cell microscopy, we identified a previously undescribed sub-nucleolar compartment, named the periphery of DFC (PDFC). Among the 12 proteins identified in PDFC, URB1 (unhealthy ribosome biogenesis 1) is required for PDFC organization and proper 3' end processing of 47S pre-rRNA. URB1 binds between the 28S rRNA and the 3' external transcribed spacer (3' ETS) to ensure 3' ETS removal, which occurs at the DFC/PDFC boundary. Loss of URB1 leads to accumulation of aberrant 3' ETS-retained 32S pre-rRNA variants, which activates exosome-dependent nucleolar surveillance. This causes decreased 28S rRNA production, reduced cell proliferation and retarded mouse embryonic pre-implementation development. Furthermore, urb1 depletion results in developmental craniofacial disorder in zebrafish, which can be at least partially rescued by further depleting exosome components. Together, this study provides new insights into functional sub-nucleolar organizations, identifies a physiologically essential step in rRNA maturation and emphasizes the exosome-dependent pre-rRNA surveillance pathway.
2023-01-04 | GSE196625 | GEO
Project description:Chromatin plays a crucial role in the intermediation between cell signaling and gene expression. The nucleolus is sensitive to stress and can orchestrate a chain of cellular events in response to stress signals. Despite being a growth factor, FGF2 has anti-proliferative and tumor-suppressive functions in some cellular contexts. In this work, we investigated how the antiproliferative effect of FGF2 modulates chromatin, nucleolus, and rDNA-associated proteins. The chromatin and nucleolar proteome indicated that FGF2 stimulation modulates proteins related to transcription regulation, particularly rRNA expression, and chromatin remodeling proteins. Upon 24 hrs of FGF2 stimulation, the global transcriptional rate and nucleolus area increased in associationalong with intense nucleolar disorganization detected by fibrillarin dispersion and electron microscopy analyses. We confirmed that FGF2 stimulation induced immature rRNA accumulation by increasing rRNA transcription regardless of changes in ribosome profiling. The rDNA-associated protein analysis reinforced that FGF2 stimulus interferes with transcription and rRNA processing/modification, since the proteins Nolc1 and Tcof1 are were upregulated after FGF2 stimulation. Changes in rRNA expression may be crucial for triggering the antiproliferative effect induced by FGF2 since inhibiting RNA Pol I, responsible for rRNA expression, partially reversed the growth arrest induced by FGF2. Taken together, we demonstrate that the antiproliferative FGF2 stimulus triggers significant transcriptional changes, and modulation modulates of the main cell transcription site, the nucleolus, directly modulating the proteome of the rDNA loci.
2022-10-11 | MSV000090511 | MassIVE