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Age-associated cryptic transcription in mammalian stem cells is linked to permissive chromatin at cryptic promoters [CMS-Seq]

ABSTRACT: Age-associated cryptic transcription in mammalian stem cells is linked to permissive chromatin at cryptic promoters [CMS-Seq]

PROVIDER: PRJNA705975 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13827157_1.fastq.gz	Fastqsanger.gz
	SRR13827157_2.fastq.gz	Fastqsanger.gz
	SRR13827158_1.fastq.gz	Fastqsanger.gz
	SRR13827158_2.fastq.gz	Fastqsanger.gz
	SRR13827159_1.fastq.gz	Fastqsanger.gz

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Age-associated cryptic transcription in mammalian stem cells is linked to permissive chromatin at cryptic promoters [CMS-Seq]

Project description:Suppressing spurious cryptic transcription by a repressive intragenic chromatin state featuring trimethylated lysine 36 on histone H3 (H3K36me3) and DNA methylation is critical for maintaining self-renewal capacity in mouse embryonic stem cells. In yeast and nematodes, such cryptic transcription is elevated with age, and reducing the levels of age-associated cryptic transcription extends yeast lifespan. Whether cryptic transcription is also increased during mammalian aging is unknown. We show for the first time an age-associated elevation in cryptic transcription in several stem cell populations, including murine hematopoietic stem cells (mHSCs) and neuronal stem cells (NSCs) and human mesenchymal stem cells (hMSCs). Using DECAP-seq, we mapped and quantified age-associated cryptic transcription in hMSCs aged in vitro. Regions with significant age-associated cryptic transcription have a unique chromatin signature: decreased H3K36me3 and increased H3K4me1, H3K4me3, and H3K27ac with age. Furthermore, genomic regions undergoing such age-dependent chromatin changes resemble known promoter sequences and are bound by the promoter-associated protein TBP even in young cells. Hence, the more permissive chromatin state at intragenic cryptic promoters likely underlies the increase of cryptic transcription in aged mammalian stem cells.

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