Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

H4K20me3 erasure facilitates reprogramming to totipotent-like state by promoting DUX4 mediated transcription [ChIP-Seq]

ABSTRACT: Epigenetic remodeling following fertilization is essential for the acquisition of embryonic totipotency. The role of H4K20me3, a key component epigenetic mark, remains largely unexplored in the context of early human embryogenesis. Here, we observed a dynamic erasure of H4K20me3 modification during zygotic genome activation (ZGA), followed by a re-establishment after ZGA in human embryos. Using in vitro reprogramming of totipotent-like states, we demonstrated transient removal of H4K20me3 in human embryonic stem cells (hESCs) promotes DUX4-mediated expression of totipotent genes, the transition into a totipotent-like state. Mechanistically, we show that H4K20me3 preferentially accumulates around genes specific to 8-cell-like (8CLC) state, which are induced by DUX4 and repressed by H4K20me3 modification. Furthermore, H4K20me3 enrichment near the pericentromeric regions may regulate satellite repeat transcripts, thereby modulating heterochromatin structure to facilitate totipotency reprogramming.

ORGANISM(S): Homo sapiens

PROVIDER: GSE287565 | GEO | 2025/05/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

H4K20me3 erasure facilitates reprogramming to totipotent-like state by promoting DUX4 mediated transcription [RNA-Seq]

Project description:Epigenetic remodeling following fertilization is essential for the acquisition of embryonic totipotency. The role of H4K20me3, a key component epigenetic mark, remains largely unexplored in the context of early human embryogenesis. Here, we observed a dynamic erasure of H4K20me3 modification during zygotic genome activation (ZGA), followed by a re-establishment after ZGA in human embryos. Using in vitro reprogramming of totipotent-like states, we demonstrated transient removal of H4K20me3 in human embryonic stem cells (hESCs) promotes DUX4-mediated expression of totipotent genes, the transition into a totipotent-like state.

2025-05-31 | GSE287564 | GEO

H4K20me3 erasure facilitates reprogramming to totipotent-like state by promoting DUX4 mediated transcription [ChIP-Seq]

Project description:H4K20me3 erasure facilitates reprogramming to totipotent-like state by promoting DUX4 mediated transcription [ChIP-Seq]

| PRJNA1213754 | ENA

H4K20me3 erasure facilitates reprogramming to totipotent-like state by promoting DUX4 mediated transcription [RNA-Seq]

Project description:H4K20me3 erasure facilitates reprogramming to totipotent-like state by promoting DUX4 mediated transcription [RNA-Seq]

| PRJNA1213755 | ENA

Dux cluster duplication ensures full activation of totipotent genes

Project description:Zygotic genome activation (ZGA) confers to the mouse two-cell (2C)embryo a unique transcriptional profile characterized by transient up-regulation of many totipotency-related genes and MERVL retrotransposons. Intriguingly, those genes are duplicated and clustered in the genome during evolution, including Dux cluster, Obox and Zscan4 family members in mice. However, the contribution and biological significance of the totipotency-related gene duplication events in early embryo development remain poorly understood. Here, we focus on Dux cluster, the master regulator of ZGA that is necessary and sufficient for the induction of 2C-like cells (2CLCs) and activation of totipotency-related genes in mouse embryonic stem cells (mESCs). By reducing Dux gene copies from 31 to 0 or 1 through CRISPR-Cas9 technology, we generate Dux-KO and Dux (n=1)mESC lines, respectively. We uncover that the totipotency-related gene transcriptional profile is awakened to a much lesser extent in Dux (n=1) mESCs compared to wild-type (WT) mESCs following global DNA demethylation reprogramming or induction of DNA damage, mimicking the intrinsic events in preimplantation development. Together, Dux cluster duplication is critically required for the full activation of ZGA transcripts.

2025-02-18 | GSE280037 | GEO

DUX4 expression in cancer induces a metastable early embryonic totipotent program

Project description:The transcription factor DUX4 regulates a portion of the zygotic gene activation (ZGA) program in the early embryo. Many cancers express DUX4 but it is unknown whether this generates cells similar to early embryonic stem cells. Here we identify cancer cell lines that express DUX4 and show that DUX4 is transiently expressed in a small subset of the cells. DUX4 expression activates the ZGA transcriptional program, the subsequent 8C-like program, and markers of early embryonic lineages; while suppressing steady-state and interferon-induced MHC class I expression. Although DUX4 was expressed in a small number of cells under standard culture conditions, DNA damage or changes in growth conditions dramatically increased the fraction of cells expressing DUX4 and its downstream programs. Demonstrating that the transient expression of endogenous DUX4 in cancer cells induces a metastable early embryonic stem cell program and suppresses antigen presentation has implications for cancer growth, progression, and immune evasion.

2023-08-09 | GSE223848 | GEO

HIRA and dPCIF1 coordinately establish totipotent chromatin and control orderly ZGA in Drosophila embryos

Project description:Early embryos undergo profound changes in their genomic architecture to establish the totipotent state, enabling pioneer factors to access chromatin and drive zygotic genome activation (ZGA). However, the mechanisms by which the totipotent state is established and properly interpreted by pioneer factors to allow orderly ZGA remain unknown. Here, we identify the H3.3-specific chaperone HIRA as a factor involving establishing totipotent-state chromatin in Drosophila early embryos. Through cophase separation with HIRA, the pioneer factor GAGA factor (GAF) efficiently binds to H3.3-marked nucleosomes to activate major-wave zygotic genes. Importantly, dPCIF1, a chromatin-associated protein, antagonized the GAF-HIRA interaction by competitively binding to HIRA, thereby restricting GAF on earlier chromatin and avoiding premature ZGA. Hence, the coordinated action of HIRA and dPCIF1 ensures sequential ZGA from the minor to major wave in early embryos. This study provides insights into understanding how a totipotent state is established and properly controlled during ZGA.

2024-11-14 | GSE253765 | GEO

Chemical-induced chromatin remodeling reprograms mouse ESCs to totipotent-like stem cells [RNA-seq]

Project description:Totipotent cells have more robust developmental potency than any other cell types, giving rise to both embryonic and extraembryonic tissues. Stable totipotent cultures and deciphering the principles of totipotency regulation would be invaluable to understand cell plasticity and lineage segregation in early development. Our approach of remodeling the pericentromeric heterochromatin and re-establishing the totipotency-specific broad H3K4me3 domains promotes the pluri-to-totipotency transition. Our protocol establishes a closer match of mouse 2-cell (2C) embryos than any other 2C-like cells. These totipotent-like stem cells (TLSCs) are stable in culture and possess unique molecular features of the mouse 2C embryo. Functionally, TLSCs are competent for germline transmission and give rise to both embryonic and extraembryonic lineages at high frequency. Therefore, TLSCs represent a highly valuable cell type for studies of totipotency and embryology.

2022-02-11 | GSE166204 | GEO

Chemical-induced chromatin remodeling reprograms mouse ESCs to totipotent-like stem cells [ChIP-seq]

2022-02-11 | GSE166208 | GEO

Chemical-induced chromatin remodeling reprograms mouse ESCs to totipotent-like stem cells [ATAC-seq]

2022-02-11 | GSE166215 | GEO

Chemical-induced chromatin remodeling reprograms mouse ESCs to totipotent-like stem cells [CUT&Tag]

2022-02-11 | GSE166210 | GEO