The effect of trisomic chromosomes on spatial genome organization and global transcription in embryonic stem cells.
Journal
Cell proliferation
ISSN: 1365-2184
Titre abrégé: Cell Prolif
Pays: England
ID NLM: 9105195
Informations de publication
Date de publication:
29 Mar 2024
29 Mar 2024
Historique:
revised:
08
03
2024
received:
20
06
2023
accepted:
14
03
2024
medline:
30
3
2024
pubmed:
30
3
2024
entrez:
30
3
2024
Statut:
aheadofprint
Résumé
Aneuploidy frequently occurs in cancer and developmental diseases such as Down syndrome, with its functional consequences implicated in dosage effects on gene expression and global perturbation of stress response and cell proliferation pathways. However, how aneuploidy affects spatial genome organization remains less understood. In this study, we addressed this question by utilizing the previously established isogenic wild-type (WT) and trisomic mouse embryonic stem cells (mESCs). We employed a combination of Hi-C, RNA-seq, chromosome painting and nascent RNA imaging technologies to compare the spatial genome structures and gene transcription among these cells. We found that trisomy has little effect on spatial genome organization at the level of A/B compartment or topologically associating domain (TAD). Inter-chromosomal interactions are associated with chromosome regions with high gene density, active histone modifications and high transcription levels, which are confirmed by imaging. Imaging also revealed contracted chromosome volume and weakened transcriptional activity for trisomic chromosomes, suggesting potential implications for the transcriptional output of these chromosomes. Our data resources and findings may contribute to a better understanding of the consequences of aneuploidy from the angle of spatial genome organization.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13639Subventions
Organisme : National Key Research and Development Program of China
ID : 2016YFA0100103
Organisme : National Key Research and Development Program of China
ID : 2021YFA1100300
Organisme : CAMS Innovation Fund for Medical Sciences
ID : 2021-I2M-1-019
Organisme : CAMS Innovation Fund for Medical Sciences
ID : 2016-I2M-3-002
Organisme : National Natural Science Foundation of China
ID : 32288102
Organisme : National Natural Science Foundation of China
ID : 32025006
Informations de copyright
© 2024 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.
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