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METTL3-dependent m6A RNA methylation represses transposable elements derived enhancers to suppress naïve pluripotency in human pluripotent stem cells

ABSTRACT: METTL3-dependent m6A RNA methylation represses transposable elements derived enhancers to suppress naïve pluripotency in human pluripotent stem cells

PROVIDER: PRJNA1152872 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30162925_1.fastq.gz	Fastqsanger.gz
	SRR30162925_2.fastq.gz	Fastqsanger.gz
	SRR30162926_1.fastq.gz	Fastqsanger.gz
	SRR30162926_2.fastq.gz	Fastqsanger.gz
	SRR30162927_1.fastq.gz	Fastqsanger.gz

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METTL3-dependent m6A RNA Methylation Regulates Transposable Elements and Represses Human Naïve Pluripotency through Transposable Element-derived Enhancers

Project description:N6-methyladenosine (m6A) is the most prevalent mRNA modification with diverse regulatory roles in mammalian cells. While its functions are well-documented in mouse embryonic stem cells (mESCs), its role in human pluripotent stem cells (hPSCs) remains to be fully explored. METTL3 is the main enzyme responsible for m6A deposition. Here, using a METTL3 inducible knockout (iKO) system, we uncovered that, unlike in mESCs, METTL3 was indispensable for hPSC maintenance. Importantly, loss of METTL3 caused significant upregulation of pluripotency factors including naïve pluripotency genes and failure to exit pluripotency, thus impaired stem cell differentiation towards embryonic and extraembryonic cells including trophoblasts. Mechanistically, METTL3 iKO in hPSCs substantially increased expression and enhancer activities of two primate-specific transposable elements (TEs), SVA_D and HERVK/LTR5_Hs, which are normally modified by METTL3-dependent m6A. METTL3 loss activated SVA_D by lowering H3K9me3 deposition, and increased chromatin accessibility at LTR5_Hs through the naïve and other pluripotency factors. Conversely, we discovered that the activated SVA_D and LTR5_Hs loci positively regulated naïve gene expression by directly interacted with their promoters. These findings thus reveal that METTL3-dependent m6A RNA methylation has critical roles in suppressing TE expression and in the human pluripotency regulatory network.

2025-05-07 | PXD056046 | Pride

METTL3-dependent m6A RNA methylation represses transposable elements derived enhancers to suppress naïve pluripotency in human pluripotent stem cells [4C]

Project description:Using a METTL3 inducible knockout (iKO) system in human expanded potential stem cells (hEPSCs), we uncovered that unlike in mESCs, METTL3 was indispensable for hPSCs’ maintenance, and that loss of METTL3 caused significant upregulation of naïve pluripotency genes accompanied with impaired hEPSCs differentiation particularly towards to both trophoblastic and amnionic lineage. Mechanistically, METTL3 iKO in hPSCs substantially increased expression of two primate-specific transposable elements (TEs), SVA_D and HERVK/LTR5_Hs.

2025-04-16 | GSE276022 | GEO

METTL3-dependent m6A RNA methylation represses transposable elements derived enhancers to suppress naïve pluripotency in human pluripotent stem cells [MeRIP-Seq]

2025-04-16 | GSE276023 | GEO

METTL3-dependent m6A RNA methylation represses transposable elements derived enhancers to suppress naïve pluripotency in human pluripotent stem cells [ATAC-seq]

2025-04-16 | GSE275948 | GEO

METTL3-dependent m6A RNA methylation represses transposable elements derived enhancers to suppress naïve pluripotency in human pluripotent stem cells [ChIP-Seq]

2025-04-16 | GSE275737 | GEO

METTL3-dependent m6A RNA methylation represses transposable elements derived enhancers to suppress naïve pluripotency in human pluripotent stem cells [RNA-Seq]

2025-04-16 | GSE274217 | GEO

METTL3-dependent m6A RNA methylation represses transposable elements derived enhancers to suppress naïve pluripotency in human pluripotent stem cells [CUT&Tag]

2025-04-16 | GSE275949 | GEO

METTL3-dependent m6A RNA methylation represses transposable elements derived enhancers to suppress naïve pluripotency in human pluripotent stem cells [4C]

Project description:METTL3-dependent m6A RNA methylation represses transposable elements derived enhancers to suppress naïve pluripotency in human pluripotent stem cells [4C]

| PRJNA1154292 | ENA

METTL3-dependent m6A RNA methylation represses transposable elements derived enhancers to suppress naïve pluripotency in human pluripotent stem cells [RNA-Seq]

Project description:METTL3-dependent m6A RNA methylation represses transposable elements derived enhancers to suppress naïve pluripotency in human pluripotent stem cells [RNA-Seq]

| PRJNA1145416 | ENA

METTL3-dependent m6A RNA methylation represses transposable elements derived enhancers to suppress naïve pluripotency in human pluripotent stem cells [ChIP-Seq]

Project description:METTL3-dependent m6A RNA methylation represses transposable elements derived enhancers to suppress naïve pluripotency in human pluripotent stem cells [ChIP-Seq]

| PRJNA1152879 | ENA

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