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Series GSE214178 Query DataSets for GSE214178
Status Public on Mar 13, 2023
Title Epigenetic dysregulation from chromosomal transit in micronuclei [MMCT ATAC-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
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.
 
Overall design ATAC-Seq on MMCT HCT116 cells from Kneissig M, et al. 2019 (clones and their parental control)
 
Contributor(s) Agustinus AS, Dameracharla B, Keuper K, Storchova Z
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
Street address 408 East 69th Street, Room 419-G
City New York
State/province New York
ZIP/Postal code 10021
Country USA
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (7)
GSM6600618 HCT116 Parental Control ATAC-Seq Biol Rep 1
GSM6600619 HCT116 Parental Control ATAC-Seq Biol Rep 2
GSM6600620 HCT116 5-17 ATAC-Seq
This SubSeries is part of SuperSeries:
GSE186589 Epigenetic dysregulation from chromosomal transit in micronuclei
Relations
BioProject PRJNA884318

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Supplementary file Size Download File type/resource
GSE214178_RAW.tar 559.0 Mb (http)(custom) TAR (of BIGWIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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