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Spatiotemporal regulation of liquid-like condensates in epigenetic inheritance

ABSTRACT: Spatiotemporal regulation of liquid-like condensates in epigenetic inheritance

PROVIDER: PRJNA439309 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6871270.fastq.gz	Fastqsanger.gz
	SRR6871261.fastq.gz	Fastqsanger.gz
	SRR6871271.fastq.gz	Fastqsanger.gz
	SRR6871262.fastq.gz	Fastqsanger.gz
	SRR6871272.fastq.gz	Fastqsanger.gz

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Spatiotemporal regulation of liquid-like condensates in epigenetic inheritance

Project description:Non-membrane bound organelles such as nucleoli, processing bodies, cajal bodies, and germ granules form via spontaneous self-assembly of specific proteins and RNAs. How these biomolecular condensates form and interact are poorly understood. Here we identify two proteins (ZNFX-1 and WAGO-4) that localize to C. elegans germ granules (P granules) in early germline blastomeres. Later in germline development, ZNFX-1/WAGO-4 separate from P granules to define an independent liquid-like condensate that we term the Z granule. In adult germ cells, Z granules assemble into ordered tri-droplet assemblages with P granules and Mutator foci that we term the PZM granule. Finally, we show that one biological function of ZNFX-1 and WAGO-4 is to interact with RNAs in the C. elegans germline to promote transgenerational epigenetic inheritance (TEI). We speculate that the temporal and spatial ordering of liquid droplet organelles may help cells organize and coordinate the complex RNA processing pathways underlying gene regulatory systems, such as RNA-directed TEI.

2018-03-21 | GSE112109 | GEO

Spatiotemporal regulation of liquid-like condensates in epigenetic inheritance.

Project description:Non-membrane-bound organelles such as nucleoli, processing bodies, Cajal bodies and germ granules form by the spontaneous self-assembly of specific proteins and RNAs. How these biomolecular condensates form and interact is poorly understood. Here we identify two proteins, ZNFX-1 and WAGO-4, that localize to Caenorhabditis elegans germ granules (P granules) in early germline blastomeres. Later in germline development, ZNFX-1 and WAGO-4 separate from P granules to define an independent liquid-like condensate that we term the Z granule. In adult germ cells, Z granules assemble into ordered tri-condensate assemblages with P granules and Mutator foci, which we term PZM granules. Finally, we show that one biological function of ZNFX-1 and WAGO-4 is to interact with silencing RNAs in the C. elegans germline to direct transgenerational epigenetic inheritance. We speculate that the temporal and spatial ordering of liquid droplet organelles may help cells to organize and coordinate the complex RNA processing pathways that underlie gene-regulatory systems, such as RNA-directed transgenerational epigenetic inheritance.

| S-EPMC6479227 | biostudies-literature

A membrane-associated condensate ensures paternal epigenetic inheritance in C. elegans

Project description:Transgenerational epigenetic inheritance (TEI) describes the transmission of gene-regulatory information across generations without altering DNA sequences. TEI allows priming of offspring towards changing environmental conditions and plays a role in the maintenance of gene silencing of selfish genetic elements like transposons. Small regulatory RNAs are well known to act in TEI, and can be transmitted via the male. Such inheritance via sperm requires dedicated mechanisms, as much of the cellular content is extruded during spermatogenesis. We identify a phase separation-based mechanism, which couples the paternal inheritance of a specific small RNA-bound silencing factor via S-palmitoylation to the transport of membranous organelles. Our findings uncover a thus far unknown paternal TEI mechanism, and describe a novel mode of transport of phase-separated condensates.

2021-03-26 | PXD019099 | Pride

ATRX Condensates Formed by Liquid-Liquid Phase Separation Regulate Neural Progenitor Cell Identity (RNA)

Project description:Alpha-thalassemia X-linked intellectual disability syndrome (ATR-X) is caused by mutations in the ATRX gene, which plays a pivotal role in heterochromatin integrity. In this study, we uncover a novel mechanism by which ATRX influences fate of human neural progenitor cells (hNPCs) through the formation of liquid-liquid phase separation (LLPS)-driven condensates. We discovered that the intrinsically disordered region (IDR) of ATRX is essential for driving LLPS, enabling ATRX to form dynamic condensates within the nucleus. The IDR region can autonomously form phase-separated droplets and recruit co-activators. In addition, formation of these condensates was crucial for the localization of ATRX at super-enhancers (SEs) in hNPCs, directly linking ATRX condensate dynamics to the regulation of gene expression critical for neural differentiation. Disruption of ATRX condensates leads to impaired neuronal differentiation, emphasizing the functional significance of ATRX in human neural development. Our findings provide new insights into the molecular function of ATRX beyond its established roles in chromatin structure, and suggest that LLPS is a key regulatory mechanism through which ATRX supports neurodevelopment. This study opens avenues for further exploration of how dysregulation of ATRX and its phase-separation ability may contribute to the pathogenesis of ATR-X syndrome and related neurodevelopmental disorders.

2025-07-13 | GSE276834 | GEO

ATRX Condensates Formed by Liquid-Liquid Phase Separation Regulate Neural Progenitor Cell Identity (ChIP)

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ATRX Condensates Formed by Liquid-Liquid Phase Separation Regulate Neural Progenitor Cell Identity

Project description:ATRX Condensates Formed by Liquid-Liquid Phase Separation Regulate Neural Progenitor Cell Identity

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PRC2 mediates paternal epigenetic inheritance

Project description:PRC2 mediates paternal epigenetic inheritance

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ATRX Condensates Formed by Liquid-Liquid Phase Separation Regulate Neural Progenitor Cell Identity (ChIP)

Project description:ATRX Condensates Formed by Liquid-Liquid Phase Separation Regulate Neural Progenitor Cell Identity (ChIP)

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ATRX Condensates Formed by Liquid-Liquid Phase Separation Regulate Neural Progenitor Cell Identity (RNA)

Project description:ATRX Condensates Formed by Liquid-Liquid Phase Separation Regulate Neural Progenitor Cell Identity (RNA)

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A nuclear pore-anchored condensate enables germ granule organisation and transgenerational epigenetic inheritance

Project description:Biomolecular condensates, such as stress and germ granules, often contain sub-compartments. For instance, the Caenorhabditis elegans germ granule, which localizes near the outer nuclear membrane of germ cell nuclei, is composed of at least four ordered compartments, each housing distinct sets of proteins and RNAs. How these compartments form and why they are spatially ordered remains poorly understood. Here, we show that the conserved RNA helicase DDX-19 defines another compartment of the larger C. elegans germ granule, which we term the D compartment. The D compartment exhibits properties of a liquid condensate and forms between the outer nuclear pore filament and other compartments of the germ granule. Two nuclear pore proteins, NPP-14 and GLEL-1, are required for its formation, suggesting that the D compartment localizes adjacent to the outer nuclear membrane via interactions with the nuclear pore. The loss of DDX-19, NPP-14, or GLEL-1 leads to functional defects, including aberrant formation of the other four germ granule compartments, a loss of germline immortality, and dysregulation of small RNA-based transgenerational epigenetic inheritance programs. Hence, we propose that a function of the D compartment is to anchor larger germ granules to nuclear pores, enabling germ granule compartmentalization and promoting transgenerational RNA surveillance.

2025-02-09 | PXD056752 | Pride

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