Peripheral blood lymphocytes with different levels of gH2AX foci and micronuclei
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE97000 | GEO | 2017/03/25
SECONDARY ACCESSION(S): PRJNA380374
REPOSITORIES: GEO
Similar Datasets
Project description:Peripheral blood lymphocytes with different levels of gH2AX foci and micronuclei
| PRJNA380374 | ENA
Project description:Baseline gene expression of human lymphocytes 24 hours after 5 Gy gamma irradiation We used microarrays to detail the global gene expression of human lymphocytes after irradiation Compare the gloable gene expression of human lymphocyte 24 hours after exposure to doses between 0 and 5 Gy γ rays
2013-04-01 | E-GEOD-44245 | biostudies-arrayexpress
Project description:DNA is strictly compartmentalised within the nucleus to prevent autoimmunity despite this cGAS, a cytosolic sensor of dsDNA, is activated in autoinflammatory disorders and by DNA damage. Precisely how cellular DNA gains access to the cytoplasm remains to be determined. Here, we report that cGAS localises to micronuclei arising from genome instability in a model of monogenic autoinflammation, after exogenous DNA damage and spontaneously in human cancer cells. These micronuclei occur after mis-segregation of DNA during cell division and consist of chromatin surrounded by their own nuclear membrane. Breakdown of the micronuclear envelope, a process associated with chromothripsis, leads to rapid accumulation of cGAS, providing a mechanism by which self-DNA becomes exposed to the cytosol. cGAS binds to and is activated by chromatin and consistent with a mitotic origin, micronuclei formation and the proinflammatory response following DNA-damage are cell-cycle dependent. Furthermore, by combining live-cell laser microdissection with single cell transcriptomics, we establish that induction of interferon stimulated gene expression occurs in micronucleated cells. We therefore conclude that micronuclei represent an important source of immunostimulatory DNA. As micronuclei formed from lagging chromosomes also activate this pathway, cGAS recognition of micronuclei may act as a cell-intrinsic immune surveillance mechanism detecting a range of neoplasia-inducing processes.
2017-07-24 | GSE100771 | GEO
Project description:H2AX phosphorylation at Ser139 (gH2AX) is an early key event of the DNA damage response (DDR) following DNA double strand breaks (DSB) induction. Although gH2AX distribution has been extensively used as a damage marker, genome-wide investigation of the subsequent DNA repair has been poorly addressed. Here we present ChIP-Seq-based distributions of Histone H3, H2AX and gH2AX under physiological conditions in HeLa cells. Additionally the same histones were studied after a single exposure to 10 Gy X-ray at 0.5, 3 and 24 hours post irradiation
2017-04-17 | GSE60526 | GEO
Project description:Chromosomal instability (CIN) and epigenetic reprograming are characteristic of advanced and metastatic human cancers, yet whether they are mechanistically linked is unknown. Here we show that missegregation of mitotic chromosomes, their sequestration in micronuclei, and subsequent micronuclear envelope rupture significantly disrupt normal histone post-translational modifications, a phenomenon conserved across humans and mice as well as cancer and non-transformed cells. Mislocalization of missegregating chromosomes during anaphase promotes loss of Histone H2B ubiquitination enrichment of histone H3 trimethylation, whereas micronuclear rupture engenders loss of histone H3 acetylation and histone H2A ubiquitination. Using fluorescence lifetime imaging, ATAC-see, and ATAC-seq we show that micronuclei exhibit profound differences in chromatin accessibility. Additionally, chromosomes that are reincorporated into the primary nucleus after transient encapsulation in micronuclei exhibit durable epigenetic dysregulation. Thus, in addition to genomic copy number alterations, CIN can serve as a vehicle for stochastic epigenetic reprogramming and heterogeneity in cancer.
2023-03-13 | GSE214448 | GEO
Project description:Biomarkers of tumour response to radiotherapy could help in optimising cancer treatment. In this study, we focus on identifying changes in extracellular miRNA as a biomarker of radiation-induced damage to human colorectal cancer cells. HCT116 cells were exposed to increasing doses of X-rays, and extracellular miRNAs were analysed by microarray. The results were correlated with frequencies of micronuclei. Fifty-nine miRNAs with positive correlation and four with negative correlation between dose (up to 6 Gy) and expression of extracellular miRNA were verified. In addition, for samples between 0 and 10 Gy, 12 miRNAs into those 59 miRNAs with positive correlation were verified. Of these, these miRNAs showed significantly positive correlation up to 10 Gy between micronucleus frequency and expression of extracellular miRNA. These results suggest that specific miRNAs could be cell damage markers and could serve as secreted radiotherapy response biomarkers for colorectal cancer; however, the results must be validated in serum samples collected from patients undergoing radiotherapy.
2021-09-16 | GSE184174 | GEO
Project description:Chromosomal instability (CIN) and epigenetic reprograming are characteristic of advanced and metastatic human cancers, yet whether they are mechanistically linked is unknown. Here we show that missegregation of mitotic chromosomes, their sequestration in micronuclei, and subsequent micronuclear envelope rupture significantly disrupt normal histone post-translational modifications, a phenomenon conserved across humans and mice as well as cancer and non-transformed cells. Mislocalization of missegregating chromosomes during anaphase promotes loss of Histone H2B ubiquitination enrichment of histone H3 trimethylation, whereas micronuclear rupture engenders loss of histone H3 acetylation and histone H2A ubiquitination. Using fluorescence lifetime imaging, ATAC-see, and ATAC-seq we show that micronuclei exhibit profound differences in chromatin accessibility. Additionally, chromosomes that are reincorporated into the primary nucleus after transient encapsulation in micronuclei exhibit durable epigenetic dysregulation. Thus, in addition to genomic copy number alterations, CIN can serve as a vehicle for stochastic epigenetic reprogramming and heterogeneity in cancer.
2023-03-13 | GSE214178 | GEO
Project description:Chromosomal instability (CIN) and epigenetic reprograming are characteristic of advanced and metastatic human cancers, yet whether they are mechanistically linked is unknown. Here we show that missegregation of mitotic chromosomes, their sequestration in micronuclei, and subsequent micronuclear envelope rupture significantly disrupt normal histone post-translational modifications, a phenomenon conserved across humans and mice as well as cancer and non-transformed cells. Mislocalization of missegregating chromosomes during anaphase promotes loss of Histone H2B ubiquitination enrichment of histone H3 trimethylation, whereas micronuclear rupture engenders loss of histone H3 acetylation and histone H2A ubiquitination. Using fluorescence lifetime imaging, ATAC-see, and ATAC-seq we show that micronuclei exhibit profound differences in chromatin accessibility. Additionally, chromosomes that are reincorporated into the primary nucleus after transient encapsulation in micronuclei exhibit durable epigenetic dysregulation. Thus, in addition to genomic copy number alterations, CIN can serve as a vehicle for stochastic epigenetic reprogramming and heterogeneity in cancer.
2023-03-13 | GSE214175 | GEO
Project description:Chromosomal instability (CIN) and epigenetic reprograming are characteristic of advanced and metastatic human cancers, yet whether they are mechanistically linked is unknown. Here we show that missegregation of mitotic chromosomes, their sequestration in micronuclei, and subsequent micronuclear envelope rupture significantly disrupt normal histone post-translational modifications, a phenomenon conserved across humans and mice as well as cancer and non-transformed cells. Mislocalization of missegregating chromosomes during anaphase promotes loss of Histone H2B ubiquitination enrichment of histone H3 trimethylation, whereas micronuclear rupture engenders loss of histone H3 acetylation and histone H2A ubiquitination. Using fluorescence lifetime imaging, ATAC-see, and ATAC-seq we show that micronuclei exhibit profound differences in chromatin accessibility. Additionally, chromosomes that are reincorporated into the primary nucleus after transient encapsulation in micronuclei exhibit durable epigenetic dysregulation. Thus, in addition to genomic copy number alterations, CIN can serve as a vehicle for stochastic epigenetic reprogramming and heterogeneity in cancer.
2023-03-13 | GSE214080 | GEO
Project description:We investigated the nuclear topography, organization and genome-wide gH2AX distribution of unrepaired DNA in rat cortical neurons 15 dyas upon X-Ray ionizing adiation (4Gy). Unrepaired DNA is confined in persistent DNA damage foci which would help preserving genome integrity. ChIp-seq analysis revealed a number of genomic regions enriched in gH2AX. Some of these regions are in close proximity to genes encoding essential proteins for neuronal function and human neurodegenerative disorders.
2019-03-23 | GSE112930 | GEO