Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Dominant mutation in Dnmt1 leads epigenetic changes (scRNAseq and snRNAseq)

ABSTRACT: A Dominant mutation in Dnmt1 leads epigenetic changes (scRNAseq and snRNAseq)

PROVIDER: PRJNA715208 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

A Dominant mutation in Dnmt1 leads epigenetic changes

Project description:A Dominant mutation in Dnmt1 leads epigenetic changes

| PRJNA715210 | ENA

A Dominant mutation in Dnmt1 leads epigenetic changes (RIPseq)

Project description:A Dominant mutation in Dnmt1 leads epigenetic changes (RIPseq)

| PRJNA784431 | ENA

A Dominant mutation in Dnmt1 leads epigenetic changes (Emseq)

Project description:A Dominant mutation in Dnmt1 leads epigenetic changes (Emseq)

| PRJNA715214 | ENA

A Dominant mutation in Dnmt1 leads epigenetic changes (rrbs)

Project description:A Dominant mutation in Dnmt1 leads epigenetic changes (rrbs)

| PRJNA715213 | ENA

A Dominant mutation in Dnmt1 leads epigenetic changes (Bulk RNAseq)

Project description:A Dominant mutation in Dnmt1 leads epigenetic changes (Bulk RNAseq)

| PRJNA748598 | ENA

A Dominant mutation in Dnmt1 leads epigenetic changes (RNA-BS-seq)

Project description:A Dominant mutation in Dnmt1 leads epigenetic changes (RNA-BS-seq)

| PRJNA784446 | ENA

DNMT1 promotes cyst growth and epigenetic age acceleration in autosomal dominant polycystic kidney disease

Project description:Alteration of DNA methylation leads to diverse diseases, and the dynamic changes of DNA methylation (DNAm) on sets of CpG dinucleotides in mammalian genomes, named as “DNAm age” and “epigenetic clocks” that can predict chronological age. However, whether and how dysregulation of DNA methylation promotes cyst progression and epigenetic age acceleration in ADPKD remains elusive. In this study, we show that DNA methyltransferase 1 (DNMT1) is upregulated in cystic renal epithelial cells and tissues, and that knockout of Dnmt1 and targeting DNMT1 with hydralazine, a safe demethylating agent, delays cyst growth in Pkd1 mutant kidneys and extends life span of Pkd1 conditional knockout mice. With methyl-CpG binding domain (MBD) protein-enriched genome sequencing (MBD-seq), DNMT1 chromatin immunoprecipitation (ChIP)-sequencing and RNA-sequencing analysis, we identify two novel DNMT1 targets, PTPRM and PTPN22 (members of the protein tyrosine phosphatase family), which function as mediators of DNMT1 and the phosphorylation and activation of PKD associated signaling pathways, including ERK, mTOR and STAT3. With whole genome bisulfide sequencing (WGBS) in ADPKD kidneys versus normal individuals, we found that the methylation of epigenetic clock associated genes were dysregulated, supporting that epigenetic age was accelerated in ADPKD kidneys. We further identify four epigenetic clock associated genes, including Hsd17b14, Mbnl1, Rassf5 and Plk2. The diverse biological roles of these four genes suggest that their methylation status may not only predict epigenetic age acceleration but also contribute to disease progression in ADPKD.

2024-06-11 | GSE257535 | GEO

Inhibition of DNMT1 methyltransferase activity via glucose-regulated O-GlcNAcylation alters the epigenome

Project description:The DNA methyltransferase activity of DNMT1 is vital for genomic maintenance of DNA methylation. We report here that DNMT1 function is regulated by O-GlcNAcylation, a protein modification that is sensitive to glucose levels, and that elevated O-GlcNAcylation of DNMT1 from high glucose environment leads to alterations to the epigenome. Using mass spectrometry and complementary alanine mutation experiments, we identified S878 as the major residue that is O-GlcNAcylated on DNMT1. Functional studies further revealed that O-GlcNAcylation of DNMT1-S878 results in an inhibition of methyltransferase activity, resulting in a general loss of DNA methylation that is preferentially at partially methylated domains (PMDs). This loss of methylation corresponds with an increase in DNA damage and apoptosis. These results establish O-GlcNAcylation of DNMT1 as a mechanism through which the epigenome is regulated by glucose metabolism and implicates a role for glycosylation of DNMT1 in metabolic diseases characterized by hyperglycemia.

2023-07-26 | PXD043031 | Pride

DNMT1 promotes cyst growth and epigenetic age acceleration in autosomal dominant polycystic kidney disease

Project description:DNMT1 promotes cyst growth and epigenetic age acceleration in autosomal dominant polycystic kidney disease

| PRJNA1080189 | ENA

A single recurrent dominant variant in ITPR3 leads to a syndromic immunodeficiency

Project description:A single recurrent dominant variant in ITPR3 leads to a syndromic immunodeficiency

| PRJEB63615 | ENA