Characterization of the dynamics of lamin A and lamin B LADs in HepG2 cells: impact of cyclosporin A
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PROVIDER: PRJNA489793 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: to qualify and quantify the rearrangement of interactions of nuclear lamins A/C and B with the genome, in relation to nuclearradial repositioning of loci and changes in gene expression, in HepG2 cells exposed to cyclosporin A. .To compare HepG2 cell line transcriptome profiling (RNA-seq) with radially positioning of the chromatin anchored at the nuclear periphery before and after CsA treatment. Methods: To this end, we mapped lamin A and lamin B lamina-associated domains (LADs) by chromatin immunoprecipitation-sequencing (ChIP-seq) of lamin A/C (antibody sc7292x, Santa Cruz Biotechnology) and lamin B1 (antibody ab16048, Abcam), respectively. HepG2 cells were either cultured under proliferative conditions (controls) or exposed for 3 days to 10 uM cyclosporin A. We also assesed the transcriptome by RNA-seq under each condition in duplicate cultures. Results: CsA elicits accumulation of pre-lamin A in HepG2 cells, raising the hypothesis of a global rearrangement of lamin-chromatin interactions. We show here the existence of overlapping and distinct lamin A and B lamina-associated domains (which we refer to as A- and B-LADs, respectively). Whereas B-LADs largely remain constitutive, CsA elicits the formation of facultative A-LADs. Re-localization of A-LADs occur mainly on preexisting B-LADs. However, LAD rearrangement does not correlate with systematic changes in gene expression within LADs. We find a reorganization of A- and B-LADs after CsA treatment, entailing distinct contributions of A- and B- type lamins. to genome organization. Indeed, classification of lamin A LADs and lamin B LADs into properties of ‘A-only’, ‘B-only’ and ‘A-B’ LADs show an overall loss of A-only LADs after CsA treatment. A- only and B-only LADs are highly dynamic with A-B LADs being more stable.The rearrangement of lamin association after CsA treatment correlates with repositioning of loci in the nuclear space with, notably, a loss of lamin B associated with a re-localization of loci towards the nuclear center and conversely, a gain of lamin B linked to a repositioning of loci towards the nuclear periphery. Predictions on radial repositioning of LADs, and of loci within, from 3D structural models of the genome were supported by fluorescence in situ hybridization (FISH) analyses. Conclusions: We show that, while they amply co-localize on well-conserved LADs, lamins A and B also interact with distinct genomic regions that can interchange (switch) between lamin A and B upon CsA treatment. We unveil distinct lamin A and B interactions with chromatin, suggesting complementary contributions to genome conformation. Our data suggest that and lamins A and B may differentially modulate genome organization.
2019-02-19 | GSE119631 | GEO
Project description:The transcriptomics changes induced in the human liver cell line HepG2 by Cyclosporin A after treatment for 12h, 24h, 48h and 72h The study investigated differential gene expression in HepG2 cell line mRNA following 12, 24, 48 and 72 hours of exposure to Cyclosporin A and solvent. Three biological replicates per compound/solvent. In total 36 arrays.
2015-01-27 | E-GEOD-45635 | biostudies-arrayexpress
Project description:The microRNA changes induced in the human liver cell line HepG2 by Cyclosporin A after treatment for 12h, 24h, 48h and 72h The study investigated differential microRNA expression in HepG2 cell line following 12, 24, 48 and 72 hours of exposure to Cyclosporin A and solvent. Three biological replicates per compound/solvent. In total 36 arrays .
2015-01-27 | E-GEOD-45800 | biostudies-arrayexpress
Project description:The transcriptomics changes induced in the human liver cell line HepG2 by Cyclosporin A after treatment for 12h, 24h, 48h and 72h
2015-01-27 | GSE45635 | GEO
Project description:The microRNA changes induced in the human liver cell line HepG2 by Cyclosporin A after treatment for 12h, 24h, 48h and 72h
2015-01-27 | GSE45800 | GEO
Project description:Background: The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions. However, the molecular machinery underlying these hierarchically organized three-dimensional (3D) chromatin architecture and dynamics remains poorly understood. Results: Here by combining imaging and sequencing, we studied the role of lamin B1 in chromatin architecture and dynamics. We found that lamin B1 depletion leads to chromatin redistribution and decompaction. Consequently, lamina-associated domains (LADs) are detached from the nuclear periphery. The inter-chromosomal interactions and overlap between chromosome territories are increased. Moreover, Hi-C data revealed that lamin B1 is required for the integrity and segregation of chromatin compartments but not for the topologically associating domains (TADs). Using live cell single molecule tracking, we further proved that depletion of lamin B1 leads to increased chromatin dynamics, owing to chromatin decompaction and redistribution toward nucleoplasm. Conclusions: Taken together, our data suggest that lamin B1 and chromatin interactions at the nuclear periphery promote LAD maintenance, genomic compartmentalization into chromosome territories and A/B compartments and confine chromatin dynamics, supporting its crucial role in chromatin higher-order structure and chromatin dynamics.
2020-11-08 | GSE124409 | GEO
Project description:We analyzed the gene expression at the onset of hair growth induced by cyclosporin A (CsA), a well-known hair growth inducer, with DNA microarray, and unveiled the step-by-step progression of hair growth. KEYWORDS: Cyclosporin A, Cyclosporine A, Ciclosporin A
2009-12-24 | GSE16739 | GEO
Project description:influence of lamin B rereceptor knockout and lamin A/C knockout on gene expression in cultured myoblast cells and in striated muscle tissue knockout samples are obtained by mating of heterozygous animals. Homozygous KO and wt animals of one litter are compared. Two boilogical replicates of KO samples are processed in parallel. wt samples are used as controls. One wt sample is processed per KO litter. Where appropriate two wt samples are used as biological replicates.
2013-01-28 | E-GEOD-37076 | biostudies-arrayexpress
Project description:influence of lamin B rereceptor knockout and lamin A/C knockout on gene expression in cultured myoblast cells and in striated muscle tissue
2013-01-28 | GSE37076 | GEO
Project description:Renal Cyclosporin-A (CsA) toxicity
| PRJNA437288 | ENA