SETDB1 regulates short interspersed nuclear elements and chromatin loop organization in mouse neural precursor cells.
Genome Biol
; 25(1): 175, 2024 Jul 03.
Article
em En
| MEDLINE
| ID: mdl-38961490
ABSTRACT
BACKGROUND:
Transposable elements play a critical role in maintaining genome architecture during neurodevelopment. Short Interspersed Nuclear Elements (SINEs), a major subtype of transposable elements, are known to harbor binding sites for the CCCTC-binding factor (CTCF) and pivotal in orchestrating chromatin organization. However, the regulatory mechanisms controlling the activity of SINEs in the developing brain remains elusive.RESULTS:
In our study, we conduct a comprehensive genome-wide epigenetic analysis in mouse neural precursor cells using ATAC-seq, ChIP-seq, whole genome bisulfite sequencing, in situ Hi-C, and RNA-seq. Our findings reveal that the SET domain bifurcated histone lysine methyltransferase 1 (SETDB1)-mediated H3K9me3, in conjunction with DNA methylation, restricts chromatin accessibility on a selective subset of SINEs in neural precursor cells. Mechanistically, loss of Setdb1 increases CTCF access to these SINE elements and contributes to chromatin loop reorganization. Moreover, de novo loop formation contributes to differential gene expression, including the dysregulation of genes enriched in mitotic pathways. This leads to the disruptions of cell proliferation in the embryonic brain after genetic ablation of Setdb1 both in vitro and in vivo.CONCLUSIONS:
In summary, our study sheds light on the epigenetic regulation of SINEs in mouse neural precursor cells, suggesting their role in maintaining chromatin organization and cell proliferation during neurodevelopment.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromatina
/
Histona-Lisina N-Metiltransferase
/
Elementos Nucleotídeos Curtos e Dispersos
/
Células-Tronco Neurais
Limite:
Animals
Idioma:
En
Revista:
Genome Biol
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Reino Unido