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Duxbl-mediated suppression of ZGA drives totipotency to pluripotency transition in mice I

ABSTRACT: Duxbl-mediated suppression of ZGA drives totipotency to pluripotency transition in mice I

PROVIDER: PRJNA882090 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21629067_1.fastq.gz	Fastqsanger.gz
	SRR21629067_2.fastq.gz	Fastqsanger.gz
	SRR21629068_1.fastq.gz	Fastqsanger.gz
	SRR21629068_2.fastq.gz	Fastqsanger.gz
	SRR21629069_1.fastq.gz	Fastqsanger.gz

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Duxbl-mediated suppression of ZGA drives totipotency to pluripotency transition in mice III

Project description:In mammalian embryos, Dux transcription factors (TF) drive a cleavage stage-specific transcriptional burst associated with zygotic genome activation (ZGA) during which hundreds of genes and endogenous retroviral (ERV) elements are transiently expressed. In mice, ZGA begins in late 1-cell (1C) embryos and is shut down within hours at the late 2-cell (2C) to 4-cell (4C) stage. While this transition is accompanied by the loss of totipotency, it is not clear whether shutdown of Dux-induced ZGA is required for this process and how ZGA is terminated. Here, we reveal an essential negative feedback axis by which the Dux family member Duxbl terminates Dux-induced ZGA from the mid 2C stage onward by direct suppression of genomic Dux target loci. Consequently, Duxbl inactivation results in sustained expression of Dux-induced ZGA leading to 4C arrest. Our study reveals the Dux/Duxbl axis that determines the timing of totipotency exit enabling the very first divergence of cell fates.

2023-12-07 | GSE213702 | GEO

Duxbl-mediated suppression of ZGA drives totipotency to pluripotency transition in mice II

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Duxbl-mediated suppression of ZGA drives totipotency to pluripotency transition in mice I

2023-12-07 | GSE213700 | GEO

Duxbl-mediated suppression of ZGA drives totipotency to pluripotency transition in mice

Project description:Duxbl-mediated suppression of ZGA drives totipotency to pluripotency transition in mice

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Duxbl-mediated suppression of ZGA drives totipotency to pluripotency transition in mice III

Project description:Duxbl-mediated suppression of ZGA drives totipotency to pluripotency transition in mice III

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Duxbl-mediated suppression of ZGA drives totipotency to pluripotency transition in mice II

Project description:Duxbl-mediated suppression of ZGA drives totipotency to pluripotency transition in mice II

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The homeobox transcription factor DUXBL controls exit from totipotency

Project description:In mice, exit from the totipotent 2-cell (2C) embryo stage requires silencing of the 2C-associated transcriptional program. However, the molecular mechanisms involved in this process remain poorly understood. Here, we demonstrate that the 2C-specific transcription factor DUX mediates an essential negative feedback loop by inducing the expression of DUXBL to promote this silencing.We show that DUXBL gains accessibility to DUX-bound regions specifically upon DUX expression.Furthermore, we determine that DUXBL interacts with TRIM24 and TRIM33, members of the tripartite motif superfamily involved in gene silencing and co-localizes with them in nuclear foci upon DUX expression. Importantly, DUXBL overexpression impairs 2C-associated transcription, whereas Duxbl inactivation in ESC increases DUX-dependent induction of the 2C-transcriptional program. Consequently, DUXBL deficiency in embryos results in sustained expression of 2C-associated transcripts, leading to early developmental arrest.Our study identifies DUXBL as an essential regulator of totipotency exit enabling the first divergence of cell fates.

2023-12-07 | GSE234053 | GEO

Duxbl-mediated suppression of ZGA drives totipotency to pluripotency transition in mice

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-12-07 | GSE213703 | GEO

The homeobox transcription factor DUXBL controls exit from totipotency

Project description:The homeobox transcription factor DUXBL controls exit from totipotency

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The homeobox transcription factor DUXBL controls exit from the totipotent 2C state [Cut&Run]

Project description:Upon exit from the totipotent 2-cell (2C) embryo stage, the 2C-associated transcriptional program needs to be efficiently silenced. However, the molecular mechanisms involved in this process remain mostly unknown. Here, we determined that the 2C-specific transcription factor DUX directly induced the expression of DUXBL to promote this silencing. CUT&RUN analysis revealed that DUXBL gained accessibility to DUX-bound regions in DUX-induced ESC while it was unable to bind those regions in uninduced cells. Importantly, DUX expression in Duxbl-knockout ESC caused increased induction of the 2C-transcriptional program, whereas DUXBL overexpression impaired 2C-associated transcription. Mechanistically, we determined that DUXBL interacted with TRIM24 and TRIM33, two members of the tripartite motif superfamily involved in gene silencing, and co-localized with them in nuclear condensates upon DUX expression. Importantly, DUXBL downregulation in mouse zygotes led to a penetrant 2C-stage arrest. Our data revealed an unexpected role for DUXBL in controlling the exit from totipotency.

2023-12-06 | GSE210890 | GEO

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