Usp17l can regulate the expression of 2C gene through Dux in mouse embryonic stem cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE277982 | GEO | 2025/06/05
REPOSITORIES: GEO
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Project description:In order to study the regulation of Usp17l on 2c gene, we overexpressed Usp17le We then performed gene expression profiling with the data obtained from the RNA-seq 48h after Usp17le overexpression .
2023-12-18 | GSE234366 | GEO
Project description:Usp17l can regulate the expression of 2C gene through Dux in mouse embryonic stem cells
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Project description:We found that H2AK119ub could regulate 2 cell genes, Usp17l could also activate 2c gene, and Usp17l could remove ubiquitination modification of H2AK119ub. Therefore, in order to determine whether Usp17l affects 2c gene transcription by regulating H2AK119ub, we knockdown Usp17l. The enrichment of H2AK119ub/H3K27me3 was detected by CUT&Tag . We also sorted out Zscan4 positive and negative cells, and detected the concentration of H3K27me3 by cut-tag
2025-02-19 | GSE224711 | GEO
Project description:Zygotic genome activation (ZGA) is the first transcription event after fertilization. A minor wave of ZGA (minor ZGA) precedes and is essential for the major wave of ZGA (major ZGA) in two-cell (2C) mouse embryos. A subset of minor ZGA genes (known as “2C” genes) are also activated in a rare population of embryonic stem cells (ESCs) (2C-like cells), which possess expanded developmental plasticity to both embryonic and extra-embryonic tissues, like 2-cell embryos. However, the functions of these 2C genes remain to be fully understood. Here, through knockdown, overexpression, and biochemical analyses, we find that one family of such 2C genes, Usp17l, plays essential roles in both transcriptional and post-translational regulation of the 2C program. Specifically, USP17LE, a member of the USP17L family, deubiquitinates H2AK119ub1 and promotes the expression of Dux and the downstream 2C genes, including Zscan4, Tcstv1, and retrotransposons such as MERVL, in ESCs. Moreover, USP17LE deubiquitinates and stabilizes ZSCAN4. In mouse pre-implantation embryos, Dux is marked by strong H2AK119ub1 at most stages except for the 1-cell and early 2-cell stages, and overexpression of Usp17le reduces H2AK119ub and further promotes the activation of Dux and 2C genes. Thus, our findings identify USP17L as a key regulator of the 2C program.
2025-06-13 | GSE282421 | GEO
Project description:Zygotic genome activation (ZGA) is the first transcription event after fertilization. A minor wave of ZGA (minor ZGA) precedes and is essential for the major wave of ZGA (major ZGA) in two-cell (2C) mouse embryos. A subset of minor ZGA genes (known as “2C” genes) are also activated in a rare population of embryonic stem cells (ESCs) (2C-like cells), which possess expanded developmental plasticity to both embryonic and extra-embryonic tissues, like 2-cell embryos. However, the functions of these 2C genes remain to be fully understood. Here, through knockdown, overexpression, and biochemical analyses, we find that one family of such 2C genes, Usp17l, plays essential roles in both transcriptional and post-translational regulation of the 2C program. Specifically, USP17LE, a member of the USP17L family, deubiquitinates H2AK119ub1 and promotes the expression of Dux and the downstream 2C genes, including Zscan4, Tcstv1, and retrotransposons such as MERVL, in ESCs. Moreover, USP17LE deubiquitinates and stabilizes ZSCAN4. In mouse pre-implantation embryos, Dux is marked by strong H2AK119ub1 at most stages except for the 1-cell and early 2-cell stages, and overexpression of Usp17le reduces H2AK119ub and further promotes the activation of Dux and 2C genes. Thus, our findings identify USP17L as a key regulator of the 2C program.
2025-06-13 | GSE282420 | GEO
Project description:In order to study the regulation of Usp17l on 2c gene, we established Usp17l knockdown cell lines KD4 and KD9. shRNA targets the common regions of the five subtypes of Usp17l We then performed gene expression profiling with the data obtained from the RNA-seq of the 7th generation cells.
2025-01-16 | GSE223067 | GEO
Project description:Usp17l affects 2c gene transcription by regulating H2AK119ub
| PRJNA932257 | ENA
Project description:Two-cell-like cells (2CLCs), a rare population (~0.5%) in murine embryonic stem cell (mESC) cultures, are in a transient totipotent-like state resembling that of 2C-stage embryos, and their discovery and characterization have greatly facilitated the study of early developmental events, such as zygotic genome activation. However, the molecular determinants governing 2C-like reprogramming remains to be elucidated. Here, we show that ZBTB24, CDCA7 and HELLS, components of a molecular pathway that is involved in the pathogenesis of immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome, function as negative regulators of 2C-like reprogramming by maintaining DNA methylation of the Dux cluster, a master inducer of the 2C-like state. Disruption of the ZBTB24-CDCA7-HELLS axis results in Dux hypomethylation and derepression, leading to dramatic upregulation of 2C-specific genes, which can be reversed by site-specific re-methylation in the Dux promoter. We also provide evidence that CDCA7 is enriched at the Dux cluster and recruits the CDCA7-HELLS chromatin remodeling complex to constitutive heterochromatin, perhaps including the perinucleolar heterochromatin, where the Dux cluster resides. Our study uncovers a key role for the ZBTB24-CDCA7-HELLS axis in safeguarding the mESC state by suppressing the 2C-like reprogramming.
2025-03-27 | GSE291998 | GEO
Project description:Two-cell-like cells (2CLCs), a rare population (~0.5%) in murine embryonic stem cell (mESC) cultures, are in a transient totipotent-like state resembling that of 2C-stage embryos, and their discovery and characterization have greatly facilitated the study of early developmental events, such as zygotic genome activation. However, the molecular determinants governing 2C-like reprogramming remains to be elucidated. Here, we show that ZBTB24, CDCA7 and HELLS, components of a molecular pathway that is involved in the pathogenesis of immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome, function as negative regulators of 2C-like reprogramming by maintaining DNA methylation of the Dux cluster, a master inducer of the 2C-like state. Disruption of the ZBTB24-CDCA7-HELLS axis results in Dux hypomethylation and derepression, leading to dramatic upregulation of 2C-specific genes, which can be reversed by site-specific re-methylation in the Dux promoter. We also provide evidence that CDCA7 is enriched at the Dux cluster and recruits the CDCA7-HELLS chromatin remodeling complex to constitutive heterochromatin. Our study uncovers a key role for the ZBTB24-CDCA7-HELLS axis in safeguarding the mESC state by suppressing the 2C-like reprogramming.
2025-04-08 | GSE290522 | GEO
Project description:The molecular regulation of zygotic genome activation (ZGA) in mammals remains poorly understood. Primed mouse embryonic stem cells contain a rare subset of “2C-like” cells that are epigenetically and transcriptionally similar to the two cell embryo and thus represent an ideal system for studying ZGA transcription regulation. Recently, the transcription factor Dux, expressed exclusively in the minor wave of ZGA, was described to activate many downstream ZGA transcripts. However, it remains unknown what upstream maternal factors initiate ZGA either in a Dux dependent or independent manner. Here we performed a candidate-based overexpression screen, identifying, amongst others, Developmental Pluripotency Associated 2 (Dppa2) and 4 (Dppa4) as positive regulators of 2C-like cells and ZGA transcription. In the germ line, promoter DNA demethylation coincides with upregulation of Dppa2 and Dppa4 which remain expressed until E7.5 when their promoters are remethylated. Furthermore, Dppa2 and Dppa4 are also expressed during iPSC reprogramming at the time 2C-like ZGA transcription transiently peaks. Through a combination of overexpression, knockdown, knockout and rescue experiments, together with transcriptional analyses, we show that Dppa2 and Dppa4 directly regulate the 2C-like cell population and associated transcripts, including Dux and the Zscan4 cluster. Importantly, we tease apart the molecular hierarchy in which the 2C-like transcriptional program is initiated and stabilised. Dppa2 and Dppa4 require Dux to initiate 2C-like ZGA transcription, suggesting they act upstream by directly regulating Dux. Supporting this, ChIP-seq analysis revealed Dppa2 and Dppa4 bind to the Dux promoter and gene body and drive its expression. Zscan4c is also able to induce 2C-like cells in wild type cells, but, in contrast to Dux, can no longer do so in Dppa2/4 double knockout cells, suggesting it may act to stabilise rather than drive the transcriptional network. Our findings suggest a model in which Dppa2/4 binding to the Dux promoter leads to Dux upregulation and activation of the 2C-like transcriptional program which is subsequently reinforced by Zscan4c.
2018-11-29 | GSE120951 | GEO