Heritable transcriptional defects from aberrations of nuclear architecture

Stamatis Papathanasiou (), Nikos A. Mynhier, Shiwei Liu, Gregory Brunette, Ema Stokasimov, Etai Jacob, Lanting Li, Caroline Comenho, Bas Steensel, Jason D. Buenrostro, Cheng-Zhong Zhang () and David Pellman ()
Additional contact information
Stamatis Papathanasiou: Blavatnik Institute, Harvard Medical School
Nikos A. Mynhier: Blavatnik Institute, Harvard Medical School
Shiwei Liu: Dana-Farber Cancer Institute
Gregory Brunette: Blavatnik Institute, Harvard Medical School
Ema Stokasimov: Blavatnik Institute, Harvard Medical School
Etai Jacob: Dana-Farber Cancer Institute
Lanting Li: Dana-Farber Cancer Institute
Caroline Comenho: Broad Institute of MIT and Harvard
Bas Steensel: The Netherlands Cancer Institute
Jason D. Buenrostro: Broad Institute of MIT and Harvard
Cheng-Zhong Zhang: Dana-Farber Cancer Institute
David Pellman: Blavatnik Institute, Harvard Medical School

Nature, 2023, vol. 619, issue 7968, 184-192

Abstract: Abstract Transcriptional heterogeneity due to plasticity of the epigenetic state of chromatin contributes to tumour evolution, metastasis and drug resistance1–3. However, the mechanisms that cause this epigenetic variation are incompletely understood. Here we identify micronuclei and chromosome bridges, aberrations in the nucleus common in cancer4,5, as sources of heritable transcriptional suppression. Using a combination of approaches, including long-term live-cell imaging and same-cell single-cell RNA sequencing (Look-Seq2), we identified reductions in gene expression in chromosomes from micronuclei. With heterogeneous penetrance, these changes in gene expression can be heritable even after the chromosome from the micronucleus has been re-incorporated into a normal daughter cell nucleus. Concomitantly, micronuclear chromosomes acquire aberrant epigenetic chromatin marks. These defects may persist as variably reduced chromatin accessibility and reduced gene expression after clonal expansion from single cells. Persistent transcriptional repression is strongly associated with, and may be explained by, markedly long-lived DNA damage. Epigenetic alterations in transcription may therefore be inherently coupled to chromosomal instability and aberrations in nuclear architecture.

Date: 2023
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41586-023-06157-7 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:619:y:2023:i:7968:d:10.1038_s41586-023-06157-7

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-023-06157-7

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().