Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A TRIM66/DAX1/Dux axis suppresses the totipotent 2-cell-like state in murine embryonic stem cells

ABSTRACT: 2 cell-like cells (2CLCs) resemble blastomeres of the 2-cell stage of embryo and are used as an in vitro model to understand the onset of zygotic genome activation (ZGA). 2CLCs comprise only ~1% of murine embryonic stem cells (mESCs). However, their specification remains unclear. Here, we show that TRIM66 restricts 2CLCs specification by repressing Dux in mESCs. Mutational assays and a solved crystal structure demonstrate that TRIM66’s PHD finger recognizes H3K4K9me3 and Bromo domain recognizes H3K18ac. Moreover, TRIM66 functions as a bridge factor to recruit the transcriptional repressor Dax1 to the Dux promoter preventing expansion of 2CLCs in mESCs. Rrecruitment of Dax1 to the Dux promoter requires TRIM66 and TRIM66’s repressive effect on Dux transcription is dependent on Dax1. Thus, beyond expanding the scope of known regulators of 2CLCs and showing TRIM66 as a chromatin-modification reader, our study suggests multiple strategies for harnessing the biotechnological and medical potential of 2CLCs.

ORGANISM(S): Mus musculus

PROVIDER: GSE169450 | GEO | 2022/06/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The disruption of CtBP regulates DUX-dependent and -independent genetic program for the 2-cell-like state in murine embryonic stem cells [RNA-seq and RRBS]

Project description:After fertilization, maternally deposited mRNA is cleared, and de novo mRNA is transcribed from the zygotic genome through zygotic genome activation (ZGA), which is called maternal-to-zygotic transition (MZT) occurring in the mouse at 2-cell (2C) stage. 2C-like cells (2CLCs) marked by MERVL expression and transcriptionally similar to 2C embryos spontaneously emerge from mouse embryonic stem cells (mESCs). Although the emergence of 2CLCs completely depends on DUX function, a recent knockout study clearly showed that DUX is dispensable for mouse embryos, suggesting that DUX-independent molecular pathways are not recapitulated in 2CLCs. We present here that the disruption of C-terminal binding protein 1/2 (Ctbp1/2) activates DUX-dependent and -independent molecular pathway associated with the development of early mouse embryos mediated by the upregulation of Preferentially expressed antigen of melanoma family-like 7 (PRAMEL7). Furthermore, the abnormality of the gene expression profile caused by Dux KO is partially rescued by the overexpression of PRAMEL7 in mESCs. Our study provides new insights into the DUX-independent molecular pathway for developing early mouse embryos.

2024-05-27 | GSE253944 | GEO

Dux cluster duplication ensures fully activation of totipotent genes

Project description:Mammalian zygotic genome activation (ZGA) following fertilization refers to the process that results in transcriptional awakening of the embryonic genome at two-cell (2C) stage in mice or 4-8 cell stage in human. ZGA confers to the mouse 2C embryo a unique transcriptional profile characterized by transient up-regulation of many totipotency-related genes and MERVL transposons. Intriguingly, many ZGA-related totipotent genes are duplicated and clustered in the genome during evolution, including Dux cluster, OBOX and Zscan4 family members in mice. Yet, the contribution and biological significance of the totipotency-related gene duplication events during evolution in totipotency acquisition remain poorly understood. Here, we focus on Dux cluster, the master regulator of ZGA that is necessary and sufficient for the emergence of 2C-like cells (2CLCs) and activation of target totipotent genes in mouse embryonic stem cells (ESCs). By reducing Dux gene copy number from 31 to 0 or 1 with CRISPR-Cas9 technology, we generated Dux-KO and Dux (n=1) ES cell lines, respectively. We found that the totipotent gene transcriptional profile could not be fully activated in Dux (n=1) mESCs compared to wild type (WT) mESCs after treatment with DNMT1 protein degrader, mimicking the DNA demethylation process during early embryo development. These data demonstrate that Dux cluster duplication is essential for fully activation of totipotency-related genes, ensuring ZGA and totipotency acquisition.

2024-10-12 | GSE263217 | GEO

ATACseq of TNG-A derived mESCs comparing WT to Dax1, Nr5a2 and Dax1/Nr5a2 knock-out clones

Project description:ATACseq in WT, Dax1, Nr5a2 and Dax1/Nr5a2 knock-out clones of mESCs in order to determine the role of the Dax1/Nr5a2 complex on chromatin accessibility and the activity of cis-regulatory elements during differentiation.<br>This experiment is part of the study: "Mechanistic framework of lineage restriction in embryonic stem cells" by Olivieri et al.

2021-03-15 | E-MTAB-9453 | biostudies-arrayexpress

DUX-miR-344-ZMYM2-mediated activation of MERVL LTRs induces a totipotent 2C-like state [RNA-seq]

Project description:Mouse embryonic stem cells (ESCs) sporadically express preimplantation two-cell-stage (2C) transcripts, including MERVL endogenous retrovirus and Zscan4 cluster genes. Such 2C-like cells (2CLCs) can contribute to both embryonic and extraembryonic tissues when reintroduced into early embryos. We examined global nucleosome occupancy and gene expression in 2CLCs and identified miR-344 as the noncoding molecule that positively controls 2CLC potency. We found that activation of endogenous MERVL or miR-344-2 alone is sufficient to induce 2CLCs with induction of 2C genes and an expanded potency. Mechanistically, miR-344 is activated by the 2C-state driver DUX and post-transcriptionally represses ZMYM2 and LSD1, which recruit the HDAC corepressor to MERVL LTR for transcriptional repression. Consistently, zygotic depletion of Zmym2 compromises the totipotency-to-pluripotency transition during early development. Our studies establish the novel DUX->miR-344--|Zmym2/Lsd1 axis that controls MERVL for expanded stem cell potency.

2020-02-06 | GSE119819 | GEO

DUX-miR-344-ZMYM2-mediated activation of MERVL LTRs induces a totipotent 2C-like state [ATAC-seq]

2020-02-06 | GSE119817 | GEO

DUX-miR-344-ZMYM2-mediated activation of MERVL LTRs induces a totipotent 2C-like state [ZMYM2 ChIP-seq]

2020-02-06 | GSE119818 | GEO

Gene expression profile after Dax1 deletion in ES cells

Project description:To investigate the function of Dax1 in mouse ES cells, whole genome microarray expression profiling was employed to identify genes that are potentially affected by the deletion of Dax1.

2015-05-13 | GSE61152 | GEO

DUX

Project description:DUX

| PRJNA930481 | ENA

ATACseq of TNG-A derived mESCs comparing WT to Dax1, Nr5a2 and Dax1/Nr5a2 knock-out clones

Project description:ATACseq of TNG-A derived mESCs comparing WT to Dax1, Nr5a2 and Dax1/Nr5a2 knock-out clones

| PRJEB39929 | ENA

Pluripotency-state-dependent Role of Dax1 in Embryonic Stem Cells Self-renewal

Project description:DAX1 (also known as Nr0b1) is regarded as an important component of the transcription factor network in mouse embryonic stem cells (ESCs). However, the role and the molecular mechanism of Dax1 in the maintenance of different pluripotency states are poorly understood. Here, we constructed a stable Dax1 knockout (KO) cell line using the CRISPR/Cas9 system to analyze the precise function of Dax1. We reported that 2i/LIF-ESCs had significantly lower Dax1 expression than LIF/serum-ESCs. Dax1KO ES cell lines could be established in 2i/LIF and their pluripotency was confirmed. In contrast, Dax1-null ESCs could not be continuously passaged in LIF/serum due to severe differentiation and apoptosis. In LIF/serum, the activities of the Core module and Myc module were significantly reduced, while the PRC2 module was activated after Dax1KO. The expression of most pro-apoptotic genes and lineage-commitment genes were drastically increased, while the down-regulated expression of anti-apoptotic genes and many pluripotency genes was observed. Our research on the pluripotent state-dependent role of Dax1 provides clues to understand the molecular regulation mechanism at different stages of early embryonic development.

2021-07-21 | GSE168423 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data