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Spatio-temporal X-linked gene reactivation in the mouse germline reveals site-specific retention of epigenetic silencing

ABSTRACT: Spatio-temporal X-linked gene reactivation in the mouse germline reveals site-specific retention of epigenetic silencing

PROVIDER: PRJNA1020766 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26161300.fastq.gz	Fastqsanger.gz
	SRR26161301.fastq.gz	Fastqsanger.gz
	SRR26161302.fastq.gz	Fastqsanger.gz
	SRR26161303.fastq.gz	Fastqsanger.gz
	SRR26161304.fastq.gz	Fastqsanger.gz

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Spatio-temporal X-linked gene reactivation in the mouse germline reveals site-specific retention of epigenetic silencing [WGBS]

Project description:Spatio-temporal X-linked gene reactivation in the mouse germline reveals site-specific retention of epigenetic silencing [WGBS]

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Spatio-temporal X-linked gene reactivation in the mouse germline reveals site-specific retention of epigenetic silencing [WGBS]

Project description:Random X-chromosome inactivation (XCI) is a hallmark of female mammalian somatic cells. This epigenetic mechanism, mediated by the long non-coding RNA Xist, occurs in the epiblast and is stably maintained to ensure proper dosage compensation of X-linked genes during life. However, this silencing is lost during primordial germ cell (PGC) development. Using a combination of single-cell allele-specific RNA sequencing and low-input chromatin profiling on in vivo developing mouse PGC, we provide unprecedented detailed maps of gene reactivation. We demonstrate that PGC still carry a fully silent X chromosome at embryonic day (E) 9.5, despite the loss of Xist expression. X-linked genes are then gradually reactivated outside the Xist first-bound regions. At E12.5, a significant part of the inactive X chromosome (Xi) still resists reactivation, carrying an epigenetic memory of its silencing. Late-reactivated genes are enriched in repressive chromatin marks, including DNA methylation and H3K27me3 marks. Our results define the timing of reactivation of the silent X chromosome a key event in female PGC reprogramming with direct implications for reproduction.

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Spatio-temporal X-linked gene reactivation in the mouse germline reveals site-specific retention of epigenetic silencing [RNA-seq]

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Project description:Spatio-temporal X-linked gene reactivation in the mouse germline reveals site-specific retention of epigenetic silencing [RNA-seq]

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Spatio-temporal X-linked gene reactivation in the mouse germline reveals site-specific retention of epigenetic silencing

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

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A method for the factor-specific spatio-temporal control of splicing

Project description:Precursor messenger RNA splicing is a highly regulated process, mediated by a complex RNA-protein machinery, the spliceosome, that encompasses several hundred proteins and five small nuclear RNAs in human. Emerging evidence suggests that the spatial organization of splicing factors and their spatio-temporal dynamics participate in the regulation of splicing. For instance, Cajal bodies and nuclear speckles function as centers for snRNP assembly and recycling or storage, respectively, whereas the assembly of spliceosomes on nascent pre-mRNAs predominantly occurs in peri-chromatin fibrils. So far, methods to manipulate the spatial distribution of splicing factors in a temporally defined manner in living cells are missing. Here, we describe such an approach that takes advantage of a reversible chemical dimerizer, and outline the requirements for efficient, reversible re-localization of splicing factors to selected sub-nuclear compartments. In a proof-of-principle study, the partial re-localization of the PRPF38A protein to the nuclear lamina induced a moderate increase in intron retention. Our approach allows fast and reversible re-localization of splicing factors, has few side effects and can be applied to any splicing factor by fusion of a protein tag through genome engineering. Apart from the systematic analysis of the spatio-temporal aspects of splicing regulation, the approach has a large potential for the fast induction and reversal of splicing switches and can reveal mechanisms of splicing regulation in native nuclear environments.

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