The ZBTB24-CDCA7-HELLS axis suppresses the totipotent 2C-like reprogramming by maintaining Dux methylation and repression DOI Creative Commons

Dan Guo,

Zeling Du,

Youqi Liu

et al.

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(7)

Published: April 10, 2025

Abstract Two-cell-like cells (2CLCs), a rare population (∼0.5%) in mouse embryonic stem cell (mESC) cultures, are transient totipotent-like state resembling that of 2C-stage embryos, and their discovery characterization have greatly facilitated the study early developmental events, such as zygotic genome activation. However, molecular determinants governing 2C-like reprogramming remain to be elucidated. Here, we show ZBTB24, CDCA7, HELLS, components pathway is involved pathogenesis immunodeficiency, centromeric instability, facial anomalies (ICF) syndrome, function negative regulators by maintaining DNA methylation Dux cluster, master inducer state. Disruption ZBTB24-CDCA7-HELLS axis results hypomethylation derepression, leading dramatic upregulation 2C-specific genes, which can reversed site-specific re-methylation promoter. We also provide evidence CDCA7 enriched at cluster recruits CDCA7–HELLS chromatin remodeling complex constitutive heterochromatin. Our uncovers key role for safeguarding mESC suppressing reprogramming.

Language: Английский

The ZBTB24-CDCA7-HELLS axis suppresses the totipotent 2C-like reprogramming by maintaining Dux methylation and repression DOI Creative Commons

Dan Guo,

Zeling Du,

Youqi Liu

et al.

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(7)

Published: April 10, 2025

Abstract Two-cell-like cells (2CLCs), a rare population (∼0.5%) in mouse embryonic stem cell (mESC) cultures, are transient totipotent-like state resembling that of 2C-stage embryos, and their discovery characterization have greatly facilitated the study early developmental events, such as zygotic genome activation. However, molecular determinants governing 2C-like reprogramming remain to be elucidated. Here, we show ZBTB24, CDCA7, HELLS, components pathway is involved pathogenesis immunodeficiency, centromeric instability, facial anomalies (ICF) syndrome, function negative regulators by maintaining DNA methylation Dux cluster, master inducer state. Disruption ZBTB24-CDCA7-HELLS axis results hypomethylation derepression, leading dramatic upregulation 2C-specific genes, which can reversed site-specific re-methylation promoter. We also provide evidence CDCA7 enriched at cluster recruits CDCA7–HELLS chromatin remodeling complex constitutive heterochromatin. Our uncovers key role for safeguarding mESC suppressing reprogramming.

Language: Английский

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