H4K20me3 erasure facilitates reprogramming to totipotent-like state by promoting DUX4 mediated transcription [RNA-Seq]
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ABSTRACT:
PROVIDER: PRJNA1213755 | ENA |
REPOSITORIES: ENA
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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. 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.
2025-05-31 | GSE287565 | GEO
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
Project description:H4K20me3 erasure facilitates reprogramming to totipotent-like state by promoting DUX4 mediated transcription [ChIP-Seq]
| PRJNA1213754 | ENA
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
Project description:DUX4 expression in cancer induces a metastable early embryonic totipotent program
| PRJNA928667 | ENA
Project description:Cellular senescence is a stable proliferation arrest and tumor suppressor mechanism. Abundance of histone modification, H4K20me3, has been reported to increase in senescent cells. Generally, H4K20me3 promotes formation of compacted transcriptionally silent constitutive heterochromatin, but its specific role in senescence is unknown. Here, we show that in senescent cells H4K20me3 is enriched at specific families of gene repeats (ZNFs, Olfactory Receptors, Protocadherins), and DNA sequences contained within senescence-associated heterochromatin (senescence-associated heterochromatin (SAHF)). Furthermore, in senescent cells, but not proliferating cells, H4K20me3 is also markedly enriched at bodies of repressed genes, including proliferation-promoting genes. Ectopic expression of SUV420H2, responsible for deposition of H4K20me3, reinforces senescence-associated proliferation arrest, and slows proliferation of transformed cells and tumorigenesis in vivo. These results indicate a dedicated role for H4K20me3 in control of nuclear organization and gene expression in senescent cells and stable senescence-associated proliferation arrest and tumor suppression.
2016-05-27 | GSE59316 | GEO
Project description:Genome-wide DNA demethylation, including the erasure of genome imprints, in primordial germ cells (PGCs), is critical as a first step for creating the totipotent epigenome in the germ line. Here, we provide evidence that contrary to the prevailing model involving active DNA demethylation, imprint erasure in mouse PGCs occurs in a manner consistent with replication-coupled passive DNA demethylation: PGCs erase imprints during their rapid proliferation with little de novo as well as maintenance DNA methylation potential and no major chromatin alterations. Our findings necessitate the re-evaluation of and provide novel insights into the mechanism of genome-wide DNA demethylation in PGCs.
2013-03-04 | GSE40412 | GEO
Project description:DUX4 and its mouse ortholog Dux are normally expressed in the early embryo—the 4 cell or 2 cell cleavage stage embryo, respectively—and activate a portion of the first wave of zygotic gene expression. DUX4 is epigenetically suppressed in nearly all somatic tissue, whereas FSHD-causing mutations result in its aberrant expression in skeletal muscle, transcriptional activation of the early embryonic program, and subsequent muscle pathology. Although DUX4 and Dux both activate an early totipotent transcriptional program, divergence of their DNA binding domains limits the use of DUX4 expressed in mice as a pre-clinical model for FSHD. In this study, we identify the porcine DUXC mRNA expressed in early development and show that both pig DUXC and human DUX4 robustly activate a highly similar early embryonic program in pig muscle cells. These results support further investigation of pig preclinical models for FSHD.
2023-05-10 | GSE210772 | GEO
Project description:The aim of this study is to define the molecular mechanisms underlying DUX4-associated toxicity in the context of facioscapulohumeral muscular dystrophy (FSHD). DUX4 is a transcription factor, which induces cell death by activating the transcription of its targets. No molecule able to directly control DUX4 activity is currently known. By using a tandem affinity purification protocol combined to mass spectrometry analysis, we identified Matrin 3 (MATR3), as the first cellular factor able to directly block DUX4 toxic activity. We found that MATR3 binds to the DNA binding domain of DUX4 blocking the activation of its genomic targets.
2023-08-21 | PXD011073 | Pride
Project description:Genome-wide DNA demethylation, including the erasure of genome imprints, in primordial germ cells (PGCs), is critical as a first step for creating the totipotent epigenome in the germ line. Here, we provide evidence that contrary to the prevailing model involving active DNA demethylation, imprint erasure in mouse PGCs occurs in a manner consistent with replication-coupled passive DNA demethylation: PGCs erase imprints during their rapid proliferation with little de novo as well as maintenance DNA methylation potential and no major chromatin alterations. Our findings necessitate the re-evaluation of and provide novel insights into the mechanism of genome-wide DNA demethylation in PGCs. We performed expression analysis of primordial germ cells (PGCs) at embryonic days 10.5-13.5. Because the number of PGCs available at these stages were low, cDNAs were amplified by the method that we previously published (Kurimoto et al. 2006, NAR 34: e42 (PMID 16547197)). To include analysis of PGC gene expression at E9.5, we re-normalized the data from our E9.5 PGC samples (GSM744103, GSM744104) from our previous publication (Hayashi et al., 2011, Cell 146: 519-32 (PMD 21820164)) together with the data from this submission.
2013-03-04 | E-GEOD-40412 | biostudies-arrayexpress