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

ABSTRACT: DUX-miR-344-ZMYM2-mediated activation of MERVL LTRs induces a totipotent 2C-like state

PROVIDER: PRJNA490363 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10733750_1.fastq.gz	Fastqsanger.gz
	SRR10733750_2.fastq.gz	Fastqsanger.gz
	SRR10733751_1.fastq.gz	Fastqsanger.gz
	SRR10733751_2.fastq.gz	Fastqsanger.gz
	SRR10733752_1.fastq.gz	Fastqsanger.gz

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DUX-miR-344-ZMYM2-mediated activation of MERVL LTRs induces a totipotent 2C-like state [ZMYM2 ChIP-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 | GSE119818 | 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 [RNA-seq]

2020-02-06 | GSE119819 | GEO

DUX-miR-344-ZMYM2-mediated activation of MERVL LTRs induces a totipotent 2C-like state [LSD1 ChIP-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 DUXmiR-344--|Zmym2/LsdSD1 axis that controls MERVL for expanded stem cell potency.

2020-02-06 | GSE142280 | GEO

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

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

| PRJNA490368 | ENA

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

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

| PRJNA490367 | ENA

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

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

| PRJNA490369 | ENA

DUX-miR-344-ZMYM2-mediated activation of MERVL LTRs induces a totipotent 2C-like state [LSD1 ChIP-seq]

Project description:DUX-miR-344-ZMYM2-mediated activation of MERVL LTRs induces a totipotent 2C-like state [LSD1 ChIP-seq]

| PRJNA596458 | ENA

DUX-miR-344-ZMYM2-Mediated Activation of MERVL LTRs Induces a Totipotent 2C-like State.

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, although the molecular mechanism underlying such an expanded 2CLC potency remains elusive. We examine global nucleosome occupancy and gene expression in 2CLCs and identified miR-344 as the noncoding molecule that positively controls 2CLC potency. We find that activation of endogenous MERVL or miR-344-2 alone is sufficient to induce 2CLCs with activation of 2C genes and an expanded potency. Mechanistically, miR-344 is activated by DUX and post-transcriptionally represses ZMYM2 and its partner LSD1, and ZMYM2 recruits LSD1/HDAC corepressor complex to MERVL LTR for transcriptional repression. Consistently, zygotic depletion of Zmym2 compromises the totipotency-to-pluripotency transition during early development. Our studies establish the previously unappreciated DUX-miR-344-Zmym2/Lsd1 axis that controls MERVL for expanded stem cell potency.

| S-EPMC8074926 | biostudies-literature

Obox4 secures zygotic genome activation upon loss of Dux

Project description:We report that the multicopy mouse homeobox gene Obox4 encodes a transcription factor that redundantly drives ZGA. OBOX4 is highly expressed in mouse 2-cell embryos. Obox4 or Dux single knockdown is tolerated by embryogenesis, whereas Obox4/Dux double knockdown completely compromises embryonic development. Genome-wide epigenetic profiling reveals that OBOX4 binds MERVL LTRs and murine endogenous retrovirus with lysine tRNA primer (MERVK) LTRs and mediates deposition of active histone modifications.

2023-08-29 | GSE196671 | GEO

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