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A family of double-homeodomain transcription factors promotes zygotic genome activation in placental mammals.

ABSTRACT: A family of double-homeodomain transcription factors promotes zygotic genome activation in placental mammals.

PROVIDER: PRJNA369387 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5219690.fastq.gz	Fastqsanger.gz
	SRR5219710_1.fastq.gz	Fastqsanger.gz
	SRR5219710_2.fastq.gz	Fastqsanger.gz
	SRR5219691.fastq.gz	Fastqsanger.gz
	SRR5219711_1.fastq.gz	Fastqsanger.gz

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A family of double-homeodomain transcription factors promotes zygotic genome activation in placental mammals [RNA-seq]

Project description:In metazoans, the fertilized embryo is transcriptionally mostly silent for a few cell divisions, until release of a first major wave of embryonic transcripts by so-called zygotic genome activation (ZGA). Maternally provided ZGA-triggering factors have been identified in Drosophila melanogaster and Danio rerio but their mammalian homologues are still undefined. Here, we reveal that DUX family transcription factors are key to this process in human and mouse. First, human Dux4 and murine Dux are expressed prior to ZGA in both species. Second, both orthologues bind to and activate the promoters of ZGA genes. Third, Dux knockdown hinders the progression of mouse embryos beyond the 2-cell stage. Fourth, it prevents the cycling of mouse embryonic stem (ES) cells through a 2-cell-like state whereas, conversely, Dux overexpression induces the accumulation of these ZGA genes-expressing ES cells. We conclude that DUX proteins are master regulators of mammalian ZGA.

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A family of double-homeodomain transcription factors promotes zygotic genome activation in placental mammals [ChIP-seq_d2]

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A family of double-homeodomain transcription factors promotes zygotic genome activation in placental mammals.

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Project description:In animal embryos, transcription is mostly silent for several cell divisions, until the release of the first major wave of embryonic transcripts through so-called zygotic genome activation (ZGA). Maternally provided ZGA-triggering factors have been identified in Drosophila melanogaster and Danio rerio, but their mammalian homologs are still undefined. Here, we provide evidence that the DUX family of transcription factors is essential to this process in mice and potentially in humans. First, human DUX4 and mouse Dux are both expressed before ZGA in their respective species. Second, both orthologous proteins bind the promoters of ZGA-associated genes and activate their transcription. Third, Dux knockout in mouse embryonic stem cells (mESCs) prevents the cells from cycling through a 2-cell-like state. Finally, zygotic depletion of Dux leads to impaired early embryonic development and defective ZGA. We conclude that DUX-family proteins are key inducers of zygotic genome activation in placental mammals.

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Project description:A conserved event of the maternal-to-zygotic transition (MZT) in animal embryos is the elimination of a subset of the maternal transcripts that accumulated during oogenesis. In invertebrates and lower vertebrates, a maternally encoded mRNA decay pathway (M-decay) acts before zygotic genome activation (ZGA) while a second pathway, which requires zygotic transcription, subsequently clears additional mRNAs (Z-decay). To date it has not been clear whether a Z-decay pathway is present in mammals. Here, we identify mouse and human maternal transcripts that are degraded after ZGA and show that inhibition of de novo transcription stabilizes these mRNAs in mouse and human embryos. We show that YAP1-TEAD4 transcription factor-mediated transcription is essential for Z-decay in mouse embryos and that TEAD4-triggered zygotic Tut4/7 expression and mRNA 3ʹ-oligouridylation direct Z-decay.

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