Similar Datasets
Project description:Chromosomal instability (CIN) and epigenetic alterations are characteristics of advanced and metastatic cancers1-4, but whether they are mechanistically linked is unknown. Here we show that missegregation of mitotic chromosomes, their sequestration in micronuclei5,6 and subsequent rupture of the micronuclear envelope7 profoundly disrupt normal histone post-translational modifications (PTMs), a phenomenon conserved across humans and mice, as well as in cancer and non-transformed cells. Some of the changes in histone PTMs occur because of the rupture of the micronuclear envelope, whereas others are inherited from mitotic abnormalities before the micronucleus is formed. Using orthogonal approaches, we demonstrate that micronuclei exhibit extensive differences in chromatin accessibility, with a strong positional bias between promoters and distal or intergenic regions, in line with observed redistributions of histone PTMs. Inducing CIN causes widespread epigenetic dysregulation, and chromosomes that transit in micronuclei experience heritable abnormalities in their accessibility long after they have been reincorporated into the primary nucleus. Thus, as well as altering genomic copy number, CIN promotes epigenetic reprogramming and heterogeneity in cancer.
| S-EPMC10322720 | biostudies-literature
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: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: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:Epigenetic dysregulation from chromosomal transit in micronuclei
| PRJNA774649 | ENA
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 | GSE214040 | 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 | GSE214012 | 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 | GSE188644 | 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 | GSE188346 | GEO