The effect of trisomic chromosomes on spatial genome organization and global transcription in embryonic stem cells.
Cell Prolif
; 57(8): e13639, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38553796
ABSTRACT
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Genoma
Limite:
Animals
Idioma:
En
Revista:
Cell Prolif
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China