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Epigenetic dysregulation from chromosomal transit in micronuclei [RPE-1 ATAC-Seq]

UID: 11146

Author(s): Raviram, Ramya

Description
Summary from GEO:

"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 from GEO:

"ATAC-Seq of p53KO or LMB2 over expressing RPE-1 cells that are either treated with vehicle control (DMSO) or reversine long term."
Subject of Study
Subject(s)
Access via GEO


Accession #: GSE186585

Access via BioProject


Accession #: PRJNA774659

Access via SRA


Accession #: SRP343176

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus, BioProject, and SRA databases provide open access to these files.
Associated Publications
Equipment Used
Illumina NovaSeq 6000
Dataset Format(s)
TAR, BED, BW
Dataset Size
1.1 GB
Data Catalog Record Updated
2024-02-14