Transcription-Associated Chromatin Reorganization During Cellular Rejuvenation
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PROVIDER: PRJNA994501 | ENA |
REPOSITORIES: ENA
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Project description:Aging is associated with a progressive decline in cellular function. To reset the aged cellular phenotype, various reprogramming approaches, including mechanical routes, have been proposed. However, the epigenetic mechanisms underlying cellular rejuvenation are poorly understood. We studied the transcriptional and genome-wide chromatin organization changes in young, aged and mechanically rejuvenated fibroblasts using RNA-seq and Hi-C experiments. The mechanically rejuvenated aged fibroblasts, that had reset their transcription to a younger cell state, showed a reorganization of the inter-chromosomal contacts and lamina-associated domains. Interestingly, the observed chromatin reorganization correlated with the transcriptional changes. Immunofluorescence experiments in the rejuvenated state confirmed increased contractility and reduced chromosome copy number variations, similar to younger fibroblasts. In addition, the rejuvenated contractile properties were maintained over multiple cell passages. Taken together, our results provide a multi-scale characterization of the chromatin reorganization that accompanies cellular aging and rejuvenation.
2024-03-20 | GSE237268 | GEO
Project description:Transcription-Associated Chromatin Reorganization During Cellular Rejuvenation (Hi-C)
| PRJNA994504 | ENA
Project description:Transcription-Associated Chromatin Reorganization During Cellular Rejuvenation (RNA-Seq)
| PRJNA994507 | ENA
Project description:Aging is associated with a progressive decline in cellular function. To reset the aged cellular phenotype, various reprogramming approaches, including mechanical routes, have been proposed. However, the epigenetic mechanisms underlying cellular rejuvenation are poorly understood. We studied the transcriptional changes in young, aged and mechanically rejuvenated fibroblasts using RNA-seq. The mechanically rejuvenated aged fibroblasts, that had reset their transcription to a younger cell state. In addition, the rejuvenated cells contractile properties were maintained over multiple cell passages. Taken together, our results provide a multi-scale characterization of the chromatin reorganization that accompanies cellular aging and rejuvenation.
2024-03-20 | GSE237269 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-03-20 | GSE237271 | GEO
Project description:Heterochromatin remodeling is critical for various cell processes. In particular, the “loss of heterochromatin” phenotype in cellular senescence engages with the progress of aging and age-related disorders. Although biological processes of senescent cells including senescence-associated heterochromatin foci (SAHF) formation, chromosome compaction and entry into senescence have been closely associated with high-order chromatin structure. the relationship between the high-order chromatin organization and the loss of heterochromatin phenotype during senescence has not been fully understood. By using senescent and late senescent fibroblasts induced by DNA damage harboring the “loss of heterochromatin” phenotype, we observed progressive 3D reorganization of heterochromatin during senescence. Facultative and constitutive heterochromatin marked by H3K27me3 and H3K9me3, respectively, showed different alterations. Facultative heterochromatin tends to switch from the repressive B-compartment to the active A-compartment, whereas constitutive heterochromatin shows no significant changes at the compartment level but enhanced interactions between themselves. Interestingly, both types show increased chromatin accessibility and gene expression leakage during senescence. Furthermore, increased chromatin accessibility in potential CTCF binding sites accompanies by the establishment of novel loops in constitutive heterochromatin. Finally, we also observed aberrant expression of repetitive elements, including LTR (long terminal repeat) and satellite classes. Overall, facultative and constitutive heterochromatin show multiscale but distinct alterations in the 3D map, meanwhile they also share the same features of increased chromatin accessibility and gene expression leakage. This study provides an epigenomic map of heterochromatin reorganization during senescence.
2019-12-31 | GSE133292 | GEO
Project description:Spermatozoa have a unique genome organization: their chromatin is almost completely devoid of histones and is formed instead of protamines which confer a high level of compaction and preserve paternal genome integrity until fertilization. Histone-to-protamine transition takes place in spermatids and is indispensable for the production of functional sperm. Here we show that the H3K79-methyltransferase DOT1L controls spermatid chromatin remodelling and subsequent reorganization and compaction of spermatozoon genome. Using a mouse model in which Dot1l is knocked-out (KO) in postnatal male germ cells, we found that Dot1l-KO sperm chromatin is less compact and has an abnormal content, characterized by the presence of transition proteins, immature protamine 2 forms and a higher level of histones. Proteomics and transcriptomics analyses performed on spermatids reveal that Dot1l-KO modifies the chromatin prior to histone removal, and leads to the deregulation of genes involved in flagellum formation and apoptosis during spermatid differentiation. As a consequence of these chromatin and gene expression defects, Dot1l-KO spermatozoa have less compact heads and are less motile, which results in impaired fertility.
2023-03-30 | PXD030734 | Pride
Project description:Proliferative and replicative senescent fibroblasts from aged human donors were reprogrammed towards pluripotency and re-differentiated in fibroblasts and then further analyzed for rejuvenation assessment. Comparison of microarrays were performed by non hierarchical clustering visualized in with Treeview software
2011-12-14 | E-GEOD-27924 | biostudies-arrayexpress
Project description:Chromatin architecture reorganization in somatic cell nuclear transfer embryos
| PRJNA608976 | ENA
Project description:Cellular senescence is a state of stable cell growth arrest induced by various stimuli such as oncogene expression and telomere shortening, referred to as oncogene-induced senescence (OIS) and replicative senescence (RS), respectively. Senescence is accompanied not only by global transcriptional alterations but also by 3D genome reorganization. Here we demonstrate that the human condensin II complex participates in cellular senescence via gene regulation and reorganization of euchromatic A and heterochromatic B chromatin compartments. OIS and RS are accompanied by A-to-B and B-to-A compartmental transitions, the latter of which occur more frequently and account for 15% of the human genome. Mechanistically, condensin is enriched at A compartments, especially at gene promoters and typical/super enhancers, and implicated in the B-to-A transitions. Genes present at B-to-A-switching regions tend to be up-regulated. The full activation of senescence genes (SASP genes and p53 targets) requires condensin; its depletion impairs senescence markers such as the activity of senescence-associated beta-galactosidase (SA-beta-gal) and senescence-associated heterochromatic foci (SAHF). This study describes that condensin reinforces euchromatic A compartments and is required for optimal expression of senescence genes, thereby contributing to the establishment and maintenance of the senescent state.
2019-11-06 | GSE118494 | GEO