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METTL3-mediated chromatin contacts promote phase separation during senescence [KAS-seq]

ABSTRACT: METTL3-mediated chromatin contacts promote phase separation during senescence [KAS-seq]

PROVIDER: PRJNA1016281 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26049145.fastq.gz	Fastqsanger.gz
	SRR26049146.fastq.gz	Fastqsanger.gz
	SRR26049147.fastq.gz	Fastqsanger.gz
	SRR26049148.fastq.gz	Fastqsanger.gz
	SRR26049149.fastq.gz	Fastqsanger.gz

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METTL3-mediated chromatin contacts promote phase separation during senescence.

Project description:METTL3-mediated chromatin contacts promote phase separation during senescence.

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METTL3-mediated chromatin contacts promote phase separation during senescence [KAS-seq]

Project description:Cellular senescence is a stable state of growth arrest that emerges as a response to stress. The methyltransferase complex (MTC) has been shown to facilitate the expression of the senescence-associated secretion phenotype (SASP) factors via genome-wide redistribution. However, whether and how MTC impacts on the three-dimensional (3D) chromatin organization and its functional implications during senescence remain largely unknown. Here we show that the MTC complex coordinates its enzymatic activity-dependent and -independent functions to enforce cellular senescence. Specifically, METTL3-mediated chromatin loops induce Hexokinase 2 (HK2) expression during senescence. The elevated HK2 expression subsequently promotes liquid-liquid phase separation (LLPS), manifesting as stress granules. These phase-separated stress granules act as reservoirs to sequester cell-cycle related mRNAs harboring polymethylated m6A sites, impeding their efficient translation. Overall, we uncover a mechanism by which senescent cells utilize phase-separated stress granules, facilitated by MTC-mediated HK2 activation, to sequester cell-cycle related mRNAs in governing senescence-associated stable growth arrest.

2024-04-22 | GSE243042 | GEO

METTL3-mediated chromatin contacts promote phase separation during senescence [Mettl3-HiChIP-seq]

Project description:METTL3-mediated chromatin contacts promote phase separation during senescence [Mettl3-HiChIP-seq]

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METTL3-mediated chromatin contacts promote phase separation during senescence [fastGro-seq]

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METTL3-mediated chromatin contacts promote phase separation during senescence [H3K27Ac-HiChIP-seq]

Project description:METTL3-mediated chromatin contacts promote phase separation during senescence [H3K27Ac-HiChIP-seq]

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METTL3-mediated chromatin contacts promote phase separation during senescence [Mettl3-HiChIP-seq]

2024-04-22 | GSE243044 | GEO

METTL3-mediated chromatin contacts promote phase separation during senescence [fastGro-seq]

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METTL3-mediated chromatin contacts promote phase separation during senescence [H3K27Ac-HiChIP-seq]

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METTL3-mediated chromatin contacts promote phase separation during senescence.

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

2024-04-22 | GSE243047 | GEO

METTL3-mediated chromatin contacts promote stress granule phase separation through metabolic reprogramming during senescence.

Project description:METTL3 is the catalytic subunit of the methyltransferase complex, which mediates m6A modification to regulate gene expression. In addition, METTL3 regulates transcription in an enzymatic activity-independent manner by driving changes in high-order chromatin structure. However, how these functions of the methyltransferase complex are coordinated remains unknown. Here we show that the methyltransferase complex coordinates its enzymatic activity-dependent and independent functions to regulate cellular senescence, a state of stable cell growth arrest. Specifically, METTL3-mediated chromatin loops induce Hexokinase 2 expression through the three-dimensional chromatin organization during senescence. Elevated Hexokinase 2 expression subsequently promotes liquid-liquid phase separation, manifesting as stress granule phase separation, by driving metabolic reprogramming. This correlates with an impairment of translation of cell-cycle related mRNAs harboring polymethylated m6A sites. In summary, our results report a coordination of m6A-dependent and -independent function of the methyltransferase complex in regulating senescence through phase separation driven by metabolic reprogramming.

| S-EPMC11208586 | biostudies-literature

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