Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

LINE-1 transposable elements regulate the exit of human pluripotency and early brain development [long-read RNA and DNA sequencing]

ABSTRACT: LINE-1 transposable elements regulate the exit of human pluripotency and early brain development [long-read RNA and DNA sequencing]

PROVIDER: PRJNA1194597 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

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

LINE-1 transposable elements regulate the exit of human pluripotency and early brain development

Project description:LINE-1 transposable elements regulate the exit of human pluripotency and early brain development

| PRJNA1194596 | ENA

LINE-1 transposable elements regulate the exit of human pluripotency and early brain development [CUT&Run]

Project description:LINE-1 transposable elements regulate the exit of human pluripotency and early brain development [CUT&Run]

| PRJNA1194600 | ENA

LINE-1 transposable elements regulate the exit of human pluripotency and early brain development [bulkRNA-seq]

Project description:LINE-1 transposable elements regulate the exit of human pluripotency and early brain development [bulkRNA-seq]

| PRJNA1194602 | ENA

LINE-1 transposable elements regulate the exit of human pluripotency and early brain development [snRNA-seq]

Project description:LINE-1 transposable elements regulate the exit of human pluripotency and early brain development [snRNA-seq]

| PRJNA1196974 | ENA

LINE-1 transposable elements regulate the exit of human pluripotency and early brain development [long-read RNA and DNA sequencing]

Project description:The mechanisms underlying primate-specific genetic programs during early human development remain poorly understood. Long interspersed nuclear element 1 (L1) is the most abundant transposable element in the human genome and represents a vast source of divergent genetic information in hominoid genomes, yet its contribution to human development is largely unknown. Using multiomics profiling, we show here that thousands of hominoid-specific L1 loci are expressed in human induced pluripotent stem cells and cerebral organoids. The transcription of unique L1 elements correlates with the absence of DNA methylation and the presence of an active epigenetic state. CRISPRi silencing of L1s revealed the presence of nearly a hundred co-opted L1-derived chimeric transcripts, and silencing of these transcripts results in altered transcription of many genes involved in neural differentiation, leading to a reduction in cerebral organoid size, implicating L1s in hominoid-specific developmental processes. In conclusion, our results show that L1-derived transcripts provide a layer of primate- and human-specific transcriptome complexity that contributes to early human developmental processes.

2025-06-20 | GSE283599 | GEO

Transposable elements are co-opted as oncogenic regulatory elements by lineage-specific transcription factors in prostate cancer

Project description:Transposable elements hold regulatory functions to impact cell fate determination by controlling gene expression, which when altered can promote oncogenesis. Despite accounting for half of the human genome, little is known about the transcriptional mechanisms that confer regulatory properties to transposable elements in pluripotent, mature versus oncogenic cell states. Through positional analysis over repetitive DNA sequence of H3K27ac ChIP-seq from 32 different normal cell and tissue states, we report pluripotent stem and mature cell states-specific “regulatory transposable elements”. Those specific to pluripotent stem cells are binding sites for the pluripotency factors NANOG, SOX2 and OCT4. In mature cell and tissue states, regulatory transposable elements are docking sites for lineage-specific transcription factors, such as AR and FOXA1 in benign prostate epithelium. Expanding the positional analysis to localized prostate tumors, we show how cancer cell states remaining dependent on AR share regulatory transposable elements with pluripotent stem cells. These include regulatory transposable elements, such as Tigger3a, that serve as binding sites for AR and whose regulatory functions are required for prostate cancer cell growth. Together, our results suggest that oncogenesis differs from normal cell fate determination by hijacking pluripotent stem cells regulatory transposable elements that serve as docking sites for lineage-specific transcription factors.

2023-09-08 | GSE224687 | GEO

Transposable Elements in Frontotemporal Lobar Degeneration

Project description:Transposable Elements in Frontotemporal Lobar Degeneration

| PRJNA561866 | ENA

Transposable Elements in Frontotemporal Lobar Degeneration

Project description:Transposable Elements in Frontotemporal Lobar Degeneration

| PRJNA561865 | ENA

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data