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| Status |
Public on Mar 13, 2023 |
| Title |
Epigenetic dysregulation from chromosomal transit in micronuclei [Chr4 ATAC-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
ATAC-Seq on RPE-1 p53KO cells that missegregates chromosome 4 during mitosis, and their control. Experiment was done in triplicates
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| Contributor(s) |
Agustinus AS, Dameracharla B, Al-Rawi D |
| Citation(s) |
37286593 |
| |
| Submission date |
Sep 26, 2022 |
| Last update date |
Jun 14, 2023 |
| Contact name |
Albert S Agustinus |
| Organization name |
Memorial Sloan Kettering Cancer Center
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| Street address |
408 East 69th Street, Room 419-G
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| City |
New York |
| State/province |
New York |
| ZIP/Postal code |
10021 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (9)
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| This SubSeries is part of SuperSeries: |
| GSE186589 |
Epigenetic dysregulation from chromosomal transit in micronuclei |
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| Relations |
| BioProject |
PRJNA884311 |
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