Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The Role of KDM2A and H3K36me2 Demethylation in Modulating MAPK Signaling during Neurodevelopment [ChIP-seq]

ABSTRACT: To investigate how KDM2A regulates downstream genes and affects NPC function and the role of KDM2A in histone methylation, we performed KDM2A and H3K36me2 ChIP-Seq. By analyzing both datasets together, we identified 2,051 overlapping peaks that were shared by both KDM2A and H3K36me2, The enriched genes were found to be associated with generating neurons, central nervous system development and cell proliferation. Furthermore, disease enrichment analysis revealed significant associations with ASD, ID and other neurodevelopmental disorders, indicating KDM2A's roles in neural development.

ORGANISM(S): Homo sapiens

PROVIDER: GSE229835 | GEO | 2024/02/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The Role of KDM2A and H3K36me2 Demethylation in Modulating MAPK Signaling during Neurodevelopment [RNA-seq]

Project description:To explore how KDM2A regulates downstream genes and impacts NPC function, we generated KDM2A knockdown H9 ESC lines using shRNA lentivirus. We designed five siRNAs and selected the two most effective ones for shRNA creation, which were then packaged into shRNA lentivirus (sh1, sh4). Subsequently, we induced these cells into NPCs and cerebral organoids. Through RNA-seq and DEG analysis, we observed that DEGs in NPCs were associated with the MAPK signaling pathway, a finding also present in cerebral organoids. We conducted a disease enrichment analysis on the obtained gene lists, revealing enrichment in neurodevelopmental disorders such as intellectual disability (ID) and autism spectrum disorder (ASD). This finding indirectly suggests that KDM2A plays a role in early neurodevelopmental processes.

2024-02-18 | GSE229834 | GEO

The Role of KDM2A and H3K36me2 Demethylation in Modulating MAPK Signaling during Neurodevelopment.

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-02-17 | GSE229836 | GEO

Genome-wide profiling of Kdm2a binding and H3K36me2 of hypoxia-cultured B cells derived from miR-155-sufficient and -deficient mice [ChIP-seq]

Project description:To investigate the impact caused by miR-155 ablation, B cells from miR-155-sufficient and -deficient mice were cultured in hypoxic conditions and analyzed for profiling the binding of a miR-155 target, Kdm2a, to genomic loci and the distribution pattern of H3K36me2, which Kdm2a demethylates.

2024-10-30 | GSE230527 | GEO

KDM2A plays a dual role in regulating the expression of malignancy-related genes in esophageal squamous cell carcinoma

Project description:KDM2A is a histone demethylase, which primarily catalyzes the demethylation of H3K36me2. Abnormal expression of KDM2A is observed in many types of cancers; however, the molecular events connected to KDM2A expression remain unclear. In this work, to gain further insight into the molecular mechanism underlying the function of KDM2A, we analyzed the expression and function of KDM2A in esophageal squamous cell carcinoma (ESCC) cells.

2023-03-31 | GSE207721 | GEO

NUF2 Drives Clear Cell Renal Cell Carcinoma by Activating HMGA2 Transcription through KDM2A-mediated H3K36me2 Demethylation.

Project description:The poor sensitivity of clear cell renal cell carcinoma (ccRCC) to conventional chemotherapy and radiotherapy makes its treatment challenging. The Ndc80 kinetochore complex component (NUF2) is involved in the development and progression of several cancers. However, its role in ccRCC remains unclear. In this study, we investigated the biological functions and underlying mechanism of NUF2 in ccRCC. We found that NUF2 expression was increased in ccRCC and associated with poor prognosis. Altering NUF2 level affected cell proliferation, migration, and invasion. Moreover, NUF2 acted as a potential oncogene to promote the progression of ccRCC through epigenetic activation of high-mobility group AT-hook 2 (HMGA2) transcription by suppressing lysine demethylase 2A expression and affecting its occupancy on the HMGA2 promoter region to regulate histone H3 lysine 36 di-methylation modification. In addition, Kaplan-Meier and multivariate analysis revealed that patients whose NUF2 and HMGA2 were both elevated showed the shortest survival; and the number of upregulated markers acted as an independent predictor to evaluate survival probability. Thus, our results demonstrate that NUF2 promotes ccRCC progression, at least partly by epigenetically regulating HMGA2 transcription, and that the NUF2-HMGA2 axis could be an ideal therapeutic target and a promising prognostic indicator for ccRCC.

| S-EPMC9254462 | biostudies-literature

Mild Glucose Starvation Induces KDM2A-Mediated H3K36me2 Demethylation through AMPK To Reduce rRNA Transcription and Cell Proliferation.

Project description:Environmental conditions control rRNA transcription. Previously, we found that serum and glucose deprivation induces KDM2A-mediated H3K36me2 demethylation in the rRNA gene (rDNA) promoter and reduces rRNA transcription in the human breast cancer cell line MCF-7. However, the molecular mechanism and biological significance are still unclear. In the present study, we found that glucose starvation alone induced the KDM2A-dependent reduction of rRNA transcription. The treatment of cells with 2-deoxy-d-glucose, an inhibitor of glycolysis, reduced rRNA transcription and H3K36me2 in the rDNA promoter, both of which were completely dependent on KDM2A in low concentrations of 2-deoxy-d-glucose, that is, mild starvation conditions. The mild starvation induced these KDM2A activities through AMP-activated kinase (AMPK) but did not affect another AMPK effector of rRNA transcription, TIF-IA. In the triple-negative breast cancer cell line MDA-MB-231, the mild starvation also reduced rRNA transcription in a KDM2A-dependent manner. We detected KDM2A in breast cancer tissues irrespective of their estrogen receptor, progesterone receptor, and HER2 status, including triple-negative cancer tissues. In both MCF-7 and MDA-MB-231 cells, mild starvation reduced cell proliferation, and KDM2A knockdown suppressed the reduction of cell proliferation. These results suggest that under mild glucose starvation AMPK induces KDM2A-dependent reduction of rRNA transcription to control cell proliferation.

| S-EPMC4648824 | biostudies-other

Transcriptome analysis of histone demethylase Kdm2a knockout in mouse embryonic stem cells

Project description:H3K36 methylation plays an important role in gene regulation. The role of H3K36 demethylase Kdm2b has been well studied. However, the role of Kdm2a in embryonic stem cells are still unkonwn. To study the function of Kdm2a in embryonic stem cells. We used CRISPR-gRNA system to knockout Kdm2a. We analyzed the gene expression change and identified target genes and repeats of Kdm2a. We uncovered a novel role of Kdm2a in regulating gene expression in embryonic stem cells.

2019-08-20 | GSE117148 | GEO

Structural basis of paralog-specific KDM2A/B nucleosome recognition

Project description:The nucleosome acidic patch is a major interaction hub for chromatin, providing a platform for enzymes to dock and orient for nucleosome-targeted activities. In order to define the molecular basis of acidic patch recognition proteome-wide, we performed an amino acid resolution acidic patch interactome screen. We discovered that the histone H3 lysine 36 (H3K36) demethylase KDM2A, but not its closely related paralog, KDM2B, requires the acidic patch for nucleosome binding. These KDM2 family JumonjiC (JmjC) domain lysine demethylases are critical to heterochromatin formation and are commonly misregulated in cancer. Despite fundamental roles in transcriptional regulation in health and disease, the molecular mechanisms governing nucleosome substrate specificity of KDM2A/B, or any other JmjC lysine demethylases, remain unclear. We used a covalent JmjC inhibitor to solve cryo-EM structures of KDM2A and KDM2B trapped in action on the nucleosome. Our structures show that KDM2-nucleosome binding is paralog-specific and facilitated by dynamic nucleosomal DNA unwrapping and histone charge shielding that mobilize the H3K36 sequence for demethylation.

2023-02-14 | PXD032791 | Pride

H3K36me2 ChIP-chip

Project description:Set2p, which mediates histone H3 Lysine 36 dimethylation (H3K36me2) in Saccharomyces cerevisiae, has been shown to associate with RNA polymerase II (RNAP II) at individual loci. Here, ChIP-chip experiments normalized to general nucleosome occupancy reveal that nucleosomes within open reading frames (ORFs) and downstream non-coding chromatin were highly dimethylated at H3K36, and that Set2p activity begins at a stereotypic distance from the initiation of transcription genome-wide. H3K36me2 is scarce in regions upstream of divergently transcribed genes, telomeres, silenced mating loci, and regions transcribed by RNA polymerase III, providing evidence that the enzymatic activity of Set2p is restricted to its association with RNAP II. The presence of H3K36me2 within ORFs correlated with the "on" or "off" state of transcription, but the degree of H3K36 dimethylation within ORFs did not correlate with transcription frequency. This provides evidence that H3K36me2 is established during the initial instances of gene transcription, with subsequent transcription having at most a maintenance role. Accordingly, newly activated genes acquire H3K36me2 in a manner that does not correlate with gene transcript levels. Finally, nucleosomes dimethylated at H3K36 appear to be refractory to loss from highly transcribed chromatin. Thus H3K36me2, which is highly conserved throughout eukaryotic evolution, provides a stable molecular mechanism for establishing chromatin context throughout the genome by distinguishing potential regulatory regions from transcribed chromatin. Keywords: ChIP-chip

2005-10-01 | GSE2991 | GEO

ASH1L links histone H3 lysine 36 di-methylation to leukemia

Project description:The histone methyltransferases MLL and ASH1L are trithorax-group proteins that interact genetically through undefined molecular mechanisms to regulate developmental and hematopoietic gene expression. Here we show that the lysine 36-dimethyl mark of histone H3 (H3K36me2) written by ASH1L is preferentially bound in vivo by LEDGF, an MLL-associated protein that co-localizes with MLL, ASH1L and H3K36me2 on chromatin genome wide. Furthermore, ASH1L facilitates recruitment of LEDGF and wild type MLL proteins to chromatin at key leukemia target genes, and is a crucial regulator of MLL-dependent transcription and leukemic transformation. Conversely KDM2A, an H3K36me2 demethylase and Polycomb-group silencing protein, antagonizes MLL-associated leukemogenesis. Our studies illuminate the molecular mechanisms underlying epigenetic interactions wherein placement, interpretation and removal of H3K36me2 contribute to the regulation of gene expression and MLL leukemia, and suggest ASH1L as a target for therapeutic intervention. Investigation of multiple transcription factors and histone modification marks in MV4-11 human leukemia cells.

2016-07-01 | E-GEOD-73528 | biostudies-arrayexpress

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