Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transient DNMT3L expression in mouse embryonic fibroblast (MEFs)

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE135258 | GEO | 2019/08/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

miRNA array profiling of Lats2 deficient mouse embryonic fibroblasts

Project description:Chromatin modifying activities for construction of appropriate epigenetic landscapes by polycomb repressive complex 2 (PRC2) play an essential role in development and tumorigenesis. However, the spatiotemporal mechanisms by which PRC2 achieves diverse epigenomes for specific tissue or cellular contexts remain poorly understood. Here, we discovered that LATS2 knockout causes dysregulation of PRC2 and subsequent transcriptome changes for differentiation in both mouse and human cells. LATS2 depletion dependent dysregulation of PRC2 also effects H3K4me3 and forms negative feedback loop for maintenance of PRC2. Further analyses reveal that LATS2 on chromatin binds to EZH2 and LATS2 has ability to phosphorylate PRC2 in vitro. These LATS2 dependent H3K27me3 targets are highly induced during neurogenesis, and statistical analysis of glioblastoma multiforme reveals that LATS2-high cases show more dedifferentiated transcriptome and poor prognosis with silencing of H3K27me3 targets. These observations suggest that LATS2-mediated epigenome coordination is pivotal for development and disease, including cancer. The rabeled cRNAs from Lats2-/- mouse embryonic fibroblasts (MEFs) and litter wild type MEFs were subjected to Agilent Mouse miRNA Microarray 8 x 15K. Each sample was run in biological dupulicate (different PDL).

2016-07-26 | E-GEOD-63532 | biostudies-arrayexpress

PRC1 Sustains the Memory of Neuronal Fate Independent of PRC2 Function

Project description:Polycomb repressive complexes (PRCs) 1 and 2 maintain stable cellular memories of early developmental patterning programs by establishing heritable patterns of gene repression. PRCs repress transcription through histone modifications and chromatin compaction, but their roles in neuronal subtype diversification are poorly defined. We unexpectedly found that PRC2 is dispensable to preserve the Hox transcription factor-dependent positional identity of spinal motor neurons (MNs), while PRC1 is essential for the specification of segmentally-restricted subtypes. Mutation of the core PRC1 component Ring1 leads to increased chromatin accessibility and ectopic expression of a broad variety of fates determinants, including Hox genes, while general features of MNs are maintained. Loss of MN subtype-specific fates in Ring1 mutants is due to the suppression of Hox networks by derepressed caudal Hox genes. These results indicate that PRC1 can function independently of de novo PRC2-dependent methylation to maintain chromatin topology and transcriptional identity at the time of differentiation.

2022-01-10 | GSE175503 | GEO

Genome-wide chromatin accessibility change after PRC2 inhibition by MAK683 treatment

Project description:The methyltransferase Polycomb Repressive Complex 2 (PRC2), composed of EZH2, SUZ12, and EED subunits, is associated with transcriptional repression via tri-methylation of histone H3 on lysine 27 residue (H3K27me3). PRC2 is a validated drug target, as the EZH2 gain-of-function mutations identified in patient samples drive tumorigenesis. PRC2 inhibitors have been discovered and demonstrated anti-cancer efficacy in clinic. However, their pharmacological mechanisms are poorly understood. MAK683 is a potent EED inhibitor in clinical development. The overall goal of our study is to understand the molecular events leading to tumor regression after PRC2 inhibition. Our study revealed that multiple senescence-associated secretory phenotype (SASP) genes, such as Gata4, Mmp2/10, Itga2 and Gbp1, are derepressed upon PRC2 inhibition and contribute to decreased Ki67+, ECM reorganization, inflammation and tumor regression even in Cdkn2a/p16 knockout tumor.

2022-03-09 | GSE183602 | GEO

H3K27me3 and H3K4me3 ChIP-seq on DMSO or MAK683 treated cancer cell

2022-03-09 | GSE183601 | GEO

RNA-seq on DMSO or MAK683 treated cancer cells and xenograft tumor samples

2022-03-09 | GSE183600 | GEO

Expression data from wild-type and Zmpste24-/- mouse embryonic fibroblasts (MEFs) at an early passage (passage 3, P3)

Project description:Zmpste24 is a metalloproteinase processing prelamin A into mature lamin A, a nuclear structure protein. Zmpste24-/- mice which accumulate prelamin A in cells recapitulate accelerated aging phenotypes observed in human premature aging disorder, Hutchinson Gilford progeria sydrome (HGPS). Zmpste24-/- mouse embryonic fibroblasts (MEFs) exhibited genomic instabiliy and accelerated aging at cellular level, which is premature senescence. We performed microarray analysis on Zmpste24-/- MEFs, compared to wild-type littermates' MEFs, at an early passage (P3), which is a pre-symptom stage before cellular senescence occurs in the mutant MEFs, in order to examine gene expression profile and figure out the underneath mechanism triggering the premature aging process. Early passage wild-type and Zmpste24-/- MEFs were collected for RNA extraction, the quality of RNAs were determinded by Electrophoresis Assay (2100 Bioanalyzer, Agilent) and RNA extractions were used for hybridization on Affymetrix microarrays.

2010-11-11 | E-GEOD-25257 | biostudies-arrayexpress

Expression data from wild-type and Zmpste24-/- mouse embryonic fibroblasts (MEFs) at an early passage (passage 3, P3)

2010-11-11 | GSE25257 | GEO

Expression data of vrn2/- emf2/+ and wild-type ovules and seeds

Project description:Polycomb Group proteins belonging to the Polycomb Repressive Complex 2 (PRC2) repress seed coat development before fertilization. Removal of PRC2 function in the integuments initiates autonomous seed coat development. We used microarrays to identify those genes that are under PRC2 control and become derepressed in mutants deficient for the PRC2 genes VRN2 and EMF2. Since vrn2 emf2 double mutants have strong developmental aberrations, we used the mutant combination vrn2/- emf2/+ .

2016-11-15 | GSE85751 | GEO

Disruption of Multiple Overlapping Functions Following Step-Wise Inactivation of the Extended Myc Network

Project description:Myc, a member of the Myc Network, supervises proliferation, metabolism and ribosomal function. The Mlx Network cross-talks with the Myc Network and regulates overlapping functions. We describe here the consequences of conditional Myc and/or Mlx gene knockouts (KOs) in primary and immortalized murine embryonic fibroblasts (MEFs). MycKO and MycKOxMlxKO “double KO” (DKO) primary MEFs, but not MlxKO MEFs, rapidly growth-arrested and displayed features of aging and senescence. In DKO MEFs, these were transient, indicating that Mlx was necessary to maintain them. KO MEFs deregulated transcripts pertaining to mitochondrial and ribosomal structure and function, cell cycle, aging, senescence and DNA damage. The expression of DNA damage-related proteins was also abnormal. Immortalized KO MEFs remained proliferation-competent but demonstrated differential sensitivities to genotoxic agents. Immortalized MycKO MEFs spontaneously developed tetraploidy that was Mlx-dependent. Different aspects of MEF aging, senescence and DNA damage responses are therefore differentially regulated by the Myc and Mlx Networks.

2023-08-28 | GSE210362 | GEO

Identification of JARID2/PRC2 interactome in human embryonic stem cells

Project description:JARID2 is an integral subunit of the chromatin modifier PRC2 (Polycomb Repressive Complex 2). PRC2 methylates lysine 27 in histone H3 and is required for human development. Mutaitons of PRC2 subunits have been frequently found in a variety of adult and pediatric cancer, suggesting that PRC2 critically regulates normal and cancer development. The goal of this project is to identify new regulator or co-factors of PRC2 and study their molecular interactions and activities in order to better understand function and regulation of PRC2 in normal and cancer development.

2020-08-04 | PXD015670 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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