GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE214448 Query DataSets for GSE214448
Status Public on Mar 13, 2023
Title Epigenetic dysregulation from chromosomal transit in micronuclei [ATAC-Seq]
Organism Mus musculus
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 4T1 cells overexpressing either dnMCAK (increased chromosomal instability) or KIF2C (decreased chromosomal instability) in triplicates
Contributor(s) Agustinus AS, Raviram R
Citation(s) 37286593
Submission date Sep 29, 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)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (6)
GSM6605927 4T1 dnMCAK ATAC biol rep 1
GSM6605928 4T1 dnMCAK ATAC biol rep 2
GSM6605929 4T1 dnMCAK ATAC biol rep 3
This SubSeries is part of SuperSeries:
GSE186589 Epigenetic dysregulation from chromosomal transit in micronuclei
BioProject PRJNA885433

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE214448_RAW.tar 1.6 Gb (http)(custom) TAR (of BED, BW, TDF)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap