Epigenetic dysregulation from chromosomal transit in micronuclei [DLD-1 CUT&RUN]

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UID: 11143

Author(s): Agustinus, Albert S.*, Dameracharla, Bhargavi, Ly, Peter, Cypher, E * MSK affiliated

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:

"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"

Subject of Study

Subject(s)

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