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Series GSE214012 Query DataSets for GSE214012
Status Public on Mar 13, 2023
Title Epigenetic dysregulation from chromosomal transit in micronuclei [DLD-1 CUT&RUN]
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 CUT&RUN using H3K4me3, H3K27me3 and H3K27ac antibodies on single cell clones DLD-1 cells that mis-segregates only the Y-chromosomes and their parental control The colones obtained from CEN-SELECT strategy from Ly et al., Nat. Genet. 2019
Contributor(s) Agustinus AS, Dameracharla B, Ly P, Cypher E
Citation(s) 37286593
Submission date Sep 23, 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)
GPL30173 NextSeq 2000 (Homo sapiens)
Samples (90)
GSM6597766 DLD-1 parental H3K4me3 biol rep 1
GSM6597767 DLD-1 parental H3K4me3 biol rep 2
GSM6597768 DLD-1 parental H3K27me3 biol rep 1
This SubSeries is part of SuperSeries:
GSE186589 Epigenetic dysregulation from chromosomal transit in micronuclei
BioProject PRJNA883635

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Supplementary file Size Download File type/resource
GSE214012_RAW.tar 7.9 Gb (http)(custom) TAR (of BW)
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Raw data are available in SRA
Processed data provided as supplementary file

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