Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PROSER1 Modulates DNA Demethylation through Dual Mechanisms to Prevent Syndromic Developmental Malformations [EM-seq]

ABSTRACT: The link between DNA methylation and neurodevelopmental disorders is well established. However, how DNA methylation is fine-tuned – ensuring precise gene expression and developmental fidelity – remains poorly understood. PROSER1, a known TET2 interactor, was recently linked to a severe neurodevelopmental disorder. Here, we demonstrate that PROSER1 interacts with all TET enzymes and stabilizes chromatin-bound TET-OGT-PROSER1-DBHS (TOPD) complexes, which regulate DNA demethylation and developmental gene expression. Surprisingly, we find that PROSER1 also sequesters TET enzymes, preventing widespread demethylation and transposable element de-repression. Our findings identify PROSER1 as a key factor which both positively and negatively regulates DNA demethylation essential for mammalian neurodevelopment.

ORGANISM(S): Mus musculus

PROVIDER: GSE273515 | GEO | 2024/11/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

PROSER1 Modulates DNA Demethylation through Dual Mechanisms to Prevent Syndromic Developmental Malformations [RNA-seq]

Project description:The link between DNA methylation and neurodevelopmental disorders is well established. However, how DNA methylation is fine-tuned – ensuring precise gene expression and developmental fidelity – remains poorly understood. PROSER1, a known TET2 interactor, was recently linked to a severe neurodevelopmental disorder. Here, we demonstrate that PROSER1 interacts with all TET enzymes and stabilizes chromatin-bound TET-OGT-PROSER1-DBHS (TOPD) complexes, which regulate DNA demethylation and developmental gene expression. Surprisingly, we find that PROSER1 also sequesters TET enzymes, preventing widespread demethylation and transposable element de-repression. Our findings identify PROSER1 as a key factor which both positively and negatively regulates DNA demethylation essential for mammalian neurodevelopment.

2024-11-21 | GSE273516 | GEO

PROSER1 Modulates DNA Demethylation through Dual Mechanisms to Prevent Syndromic Developmental Malformations [ChIP-seq]

2024-11-20 | GSE273514 | GEO

The proline and serine rich protein PROSER1 mediates O-GlcNAcylation of TET2 to regulate DNA demethylation on UTX-dependent enhancers and CpG islands [WGBS]

Project description:DNA methylation at enhancers and CpG islands usually leads to gene repression, which is counteracted by DNA demethylation through the TET protein family. However, how TET enzymes are recruited and regulated at these genomic loci is not fully understood. Here, we identify TET2 and a previously undescribed proline and serine rich protein, PROSER1 as interactors of UTX, a component of the enhancer-associated MLL3/4 complexes. Affinity purification of PROSER1 resulted in the identification of OGT and TET1-3. We find that PROSER1 mediates the interaction between OGT and TET2, thus promoting TET2 O-GlcNAcylation and protein stability. Additionally, PROSER1, UTX, OGT, and TET1/2 colocalize on many genomic elements genome-wide. Loss of PROSER1 results in lower enrichment of UTX, and TET1/2 at enhancers and CpG islands, with a concomitant increase in DNA methylation and transcriptional downregulation of associated target genes and increased DNA hypermethylation encroachment at H3K4me1-predisposed CpG islands. Taken together, this study describes for the first time a regulator of TET2 O-GlcNAcylation and its implications in mediating DNA demethylation at UTX-dependent enhancers and CpG islands.

2021-10-13 | GSE172143 | GEO

The proline and serine rich protein PROSER1 mediates O-GlcNAcylation of TET2 to regulate DNA demethylation on UTX-dependent enhancers and CpG islands [RNA-seq]

2021-10-13 | GSE172144 | GEO

The proline and serine rich protein PROSER1 mediates O-GlcNAcylation of TET2 to regulate DNA demethylation on UTX-dependent enhancers and CpG islands [hMeDIP-seq]

2021-10-13 | GSE172142 | GEO

The proline and serine rich protein PROSER1 mediates O-GlcNAcylation of TET2 to regulate DNA demethylation on UTX-dependent enhancers and CpG islands [ChIP-seq]

2021-10-13 | GSE172141 | GEO

PROSER1 Modulates DNA Demethylation through Dual Mechanisms to Prevent Syndromic Developmental Malformations [EM-seq]

Project description:PROSER1 Modulates DNA Demethylation through Dual Mechanisms to Prevent Syndromic Developmental Malformations [EM-seq]

| PRJNA1142190 | ENA

PROSER1 Modulates DNA Demethylation through Dual Mechanisms to Prevent Syndromic Developmental Malformations

Project description:PROSER1 Modulates DNA Demethylation through Dual Mechanisms to Prevent Syndromic Developmental Malformations