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Nr5a2 is dispensable for ZGA but essential for morula development [ATAC-seq]

ABSTRACT: Nr5a2 is dispensable for ZGA but essential for morula development [ATAC-seq]

PROVIDER: PRJNA1111798 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29034727.fastq.gz	Fastqsanger.gz
	SRR29034728.fastq.gz	Fastqsanger.gz
	SRR29034729.fastq.gz	Fastqsanger.gz
	SRR29034730.fastq.gz	Fastqsanger.gz
	SRR29034731.fastq.gz	Fastqsanger.gz

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Nr5a2 is dispensable for ZGA but essential for morula development

Project description:Nr5a2 is dispensable for ZGA but essential for morula development

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Nr5a2 is dispensable for ZGA but essential for morula development [RNA-seq]

Project description:Early embryogenesis is driven by transcription factors (TFs) that first activate the zygotic genome and then specify the lineages constituting the blastocyst. While the TFs specifying the blastocyst’s lineages are well characterised, those playing earlier roles are ill-defined. Using mouse models of the TF Nr5a2, we show that Nr5a2-/- embryos arrest at the early morula stage and exhibit overt phenotypical problems such as altered lineage specification, frequent mitotic failure and substantial chromosome segregation defects. Transcriptomic profiling shows that Nr5a2 is a master regulator required for appropriate expression of thousands of genes at the 8-cells stage, including lineage-specifying TFs and genes involved in mitosis, telomere maintenance and DNA repair. We conclude that Nr5a2 coordinates proliferation, genome stability and lineage specification to ensure proper morula development.

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Nr5a2 is dispensable for ZGA but essential for morula development [ATAC-seq]

Project description:Early embryogenesis is driven by transcription factors (TFs) that first activate the zygotic genome and then specify the lineages constituting the blastocyst. While the TFs specifying the blastocyst’s lineages are well characterised, those playing earlier roles are ill-defined. Using mouse models of the TF Nr5a2, we show that Nr5a2-/- embryos arrest at the early morula stage and exhibit overt phenotypical problems such as altered lineage specification, frequent mitotic failure and substantial chromosome segregation defects. We further show that whilst NR5A2 plays a minor but measurable role during zygotic genome activation, it predominantly acts as a master regulator at the 8-cells stage, controlling expression of lineage-specifying TFs and genes involved in mitosis, telomere maintenance and DNA repair. We conclude that NR5A2 coordinates proliferation, genome stability and lineage specification to ensure proper morula development.

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Nr5a2 is dispensable for ZGA but essential for morula development

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Zygotic genome activation by the totipotency pioneer factor Nr5a2

Project description:Life begins with a switch in genetic control from the maternal to the embryonic genome during zygotic genome activation (ZGA). Despite its importance, the essential regulators of ZGA remain largely unknown in mammals. Based on de novo motif searches, we identified the orphan nuclear receptor Nr5a2 as a key activator of major ZGA in mouse 2-cell embryos. Nr5a2 is required for progression beyond the 2-cell stage. It binds to its motif within SINE B1/Alu retrotransposable elements found in cis-regulatory regions of ZGA genes. Chemical inhibition suggests that 72% of ZGA genes are regulated by Nr5a2 and potentially other orphan nuclear receptors. Nr5a2 promotes chromatin accessibility during ZGA and binds nucleosomal DNA in vitro. We conclude that Nr5a2 is an essential pioneer factor that regulates ZGA.

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