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Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome [PBAT BS-Seq]

ABSTRACT: Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome [PBAT BS-Seq]

PROVIDER: PRJNA1106285 | ENA |

REPOSITORIES: ENA

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Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome [PBAT BS-Seq]

Project description:The placental DNA methylation landscape is unique, with widespread partially methylated domains (PMDs) and hundreds of placental-specific imprinted domains. Furthermore, the placental ‘methylome’ has been the focus of extensive study for links with pregnancy complications. Human trophoblast stem cells (hTSCs) offer exciting potential for functional epigenetic studies; however, whether the hTSC epigenome recapitulates primary cytotrophoblast, remains poorly described. In this study, we demonstrate that hTSCs exhibit an atypical methylome, with DNA methylation present over transcribed gene bodies but a complete loss of placental PMDs. Using single-cell RNA-seq from human embryogenesis, hTSCs display a notable absence of DNMT3L expression. Ectopic expression of DNMT3L in hTSCs restored placental PMDs. DNMT3L-expressing hTSCs showed comparable stemness but failed to syncytialise in organoid culture, associated with hypermethylation of STB transcription factor motifs. These findings reveal that DNMT3L is essential in establishing the human placental methylome and that DNMT3L downregulation is necessary for successful trophoblast differentiation.

2025-01-08 | GSE266195 | GEO

Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome [RNA-seq]

2025-01-08 | GSE266193 | GEO

Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome [ChIP-seq]

2025-01-08 | GSE266194 | GEO

Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome.

Project description:Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome.

| PRJNA1106282 | ENA

Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome [ChIP-seq]

Project description:Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome [ChIP-seq]

| PRJNA1106286 | ENA

Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome [RNA-seq]

Project description:Ectopic expression of DNMT3L in human trophoblast stem cells restores features of the placental methylome [RNA-seq]

| PRJNA1106284 | ENA

ONSET BS Seq

Project description:DNA was isolated from E5.5 mouse embryos, for Epiblast, Visceral Endoderm, and Extraembryonic Endoderm, and BS-Seq libraries generated using the PBAT approach. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

2014-12-23 | E-ERAD-316 | biostudies-arrayexpress

Transient DNMT3L expression in mouse embryonic fibroblast (MEFs)

Project description:Global heterochromatin reduction, which is one of the hallmarks of aging cells, is associated with reduced transposable element repression and increased risk of chromatin instability. To ensure genomic integrity, the irreparable cells in a population exit permanently from the cell cycle, and this process is termed “senescence”. However, senescence only blocks the expansion of unwanted cells, and the aberrant chromatin of senescent cells remains unstable. Serendipitously, we found that the transient ectopic expression of a repressive epigenetic modulator, DNA methyltransferase 3-like (DNMT3L) was sufficient to delay the premature senescence progression of late-passage mouse embryonic fibroblasts (MEFs) associated with a tightened global chromatin structure. DNMT3L induces more repressive H3K9 methylation on endogenous retroviruses and downregulates the derepressed transposons in aging MEFs. In addition, we found that a pulse of ectopic DNMT3L resulted in the reestablishment of H3K27me3 on polycomb repressive complex 2 (PRC2)-target genes that were derepressed in old MEFs. We demonstrated that ectopic DNMT3L interacted with PRC2 in MEFs. Our data also suggested that ectopic DNMT3L might guide PRC2 to redress deregulated chromatin regions in aging cells. This study might lead to an epigenetic reinforcement strategy for overcoming aging-associated epimutation and senescence.

2019-08-02 | GSE135258 | GEO

An ectopic enhancer restores CFTR expression through de novo chromatin looping.

Project description:An ectopic enhancer restores CFTR expression through de novo chromatin looping.

| PRJNA841375 | ENA

Biodegradation of PBAT: Tracking the assimilation of labelled carbon

Project description:The use of carbon labelled PBAT units allowed us to follow biodegradation of all PBAT building blocks. The presented workflow is a novel approach to study the fundamental steps in polymer biodegradation in complex systems.

2023-07-27 | PXD039265 | Pride

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