Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Heterozygous Kmt2d loss diminishes enhancers to render medulloblastoma cells vulnerable to combinatory inhibition of lysine demethylation and oxidative phosphorylation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE248458 | GEO | 2025/06/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Heterozygous Kmt2d loss diminishes enhancers to render medulloblastoma cells vulnerable to combinatory inhibition of lysine demethylation and oxidative phosphorylation [RNA-seq]

Project description:The histone methyltransferase KMT2D (alias MLL4) is frequently mutated in medulloblastoma (MB). Heterozygous loss of KMT2D is prevalent in MB. However, the role of heterozygous KMT2D loss remains unknown. Here, we show that heterozygous Kmt2d loss highly promotes Ptch+/–-driven MB genesis in mice. Heterozygous Kmt2d loss upregulated tumor-promoting programs, including oxidative phosphorylation (OXPHOS), in Ptch+/–-driven MB genesis. Heterozygous Kmt2d loss extensively diminished enhancer signals and H3K4me3 signature, including those for transcription-repressive tumor suppressor genes (e.g., Ncor2). NCOR2 repressed the expression of tumor-promoting genes. Combinatory pharmacological inhibition of OXPHOS and the enhancer-decommissioning demethylase LSD1 drastically reduced the tumorigenicity of MB cells bearing heterozygous Kmt2d loss. These findings reveal the mechanistic basis underlying the MB-promoting effect of heterozygous KMT2D loss.

2025-06-02 | GSE293811 | GEO

Heterozygous Kmt2d loss diminishes enhancers to render medulloblastoma cells vulnerable to combinatory inhibition of lysine demethylation and oxidative phosphorylation [ChIP-Seq]

2025-06-02 | GSE248457 | GEO

Heterozygous Kmt2d loss diminishes enhancers to render medulloblastoma cells vulnerable to combinatory inhibition of lysine demethylation and oxidative phosphorylation [CUT&RUN]

2025-06-02 | GSE248456 | GEO

Heterozygous Kmt2d loss diminishes enhancers to render medulloblastoma cells vulnerable to combinatory inhibition of lysine demethylation and oxidative phosphorylation

Project description:Heterozygous Kmt2d loss diminishes enhancers to render medulloblastoma cells vulnerable to combinatory inhibition of lysine demethylation and oxidative phosphorylation

| PRJNA1044050 | ENA

Heterozygous Kmt2d loss diminishes enhancers to render medulloblastoma cells vulnerable to combinatory inhibition of lysine demethylation and oxidative phosphorylation [RNA-seq]

Project description:Heterozygous Kmt2d loss diminishes enhancers to render medulloblastoma cells vulnerable to combinatory inhibition of lysine demethylation and oxidative phosphorylation [RNA-seq]

| PRJNA1246494 | ENA

Heterozygous Kmt2d loss diminishes enhancers to render medulloblastoma cells vulnerable to combinatory inhibition of lysine demethylation and oxidative phosphorylation [ChIP-Seq]

| PRJNA1044059 | ENA

Heterozygous Kmt2d loss diminishes enhancers to render medulloblastoma cells vulnerable to combinatory inhibition of lysine demethylation and oxidative phosphorylation [CUT&RUN]

| PRJNA1044057 | ENA

Histone H3 lysine 4 methyltransferase KMT2D.

Project description:Histone-lysine N-methyltransferase 2D (KMT2D), also known as MLL4 and MLL2 in humans and Mll4 in mice, belongs to a family of mammalian histone H3 lysine 4 (H3K4) methyltransferases. It is a large protein over 5500 amino acids in size and is partially functionally redundant with KMT2C. KMT2D is widely expressed in adult tissues and is essential for early embryonic development. The C-terminal SET domain is responsible for its H3K4 methyltransferase activity and is necessary for maintaining KMT2D protein stability in cells. KMT2D associates with WRAD (WDR5, RbBP5, ASH2L, and DPY30), NCOA6, PTIP, PA1, and H3K27 demethylase UTX in one protein complex. It acts as a scaffold protein within the complex and is responsible for maintaining the stability of UTX. KMT2D is a major mammalian H3K4 mono-methyltransferase and co-localizes with lineage determining transcription factors on transcriptional enhancers. It is required for the binding of histone H3K27 acetyltransferases CBP and p300 on enhancers, enhancer activation and cell-type specific gene expression during differentiation. KMT2D plays critical roles in regulating development, differentiation, metabolism, and tumor suppression. It is frequently mutated in developmental diseases, such as Kabuki syndrome and congenital heart disease, and various forms of cancer. Further understanding of the mechanism through which KMT2D regulates gene expression will reveal why KMT2D mutations are so harmful and may help generate novel therapeutic approaches.

| S-EPMC5546304 | biostudies-literature

Novel heterozygous variants in KMT2D associated with holoprosencephaly.

Project description:Lysine methyltransferase 2D (KMT2D; OMIM 602113) encodes a histone methyltransferase involved in transcriptional regulation of the beta-globin and estrogen receptor as part of a large protein complex known as activating signal cointegrator-2-containing complex (ASCOM). Heterozygous germline mutations in the KMT2D gene are known to cause Kabuki syndrome (OMIM 147920), a developmental multisystem disorder. Neither holoprosencephaly nor other defects in human forebrain development have been previously associated with Kabuki syndrome. Here we report two patients diagnosed with alobar holoprosencephaly in their antenatal period with de novo monoallelic KMT2D variants identified by trio-based exome sequencing. The first patient was found to have a stop-gain variant c.12565G>T (p.Gly4189*), while the second patient had a missense variant c.5A>G (p.Asp2Gly). Phenotyping of each patient did not reveal any age-related feature of Kabuki syndrome. These two cases represent the first report on association between KMT2D and holoprosencephaly.

| S-EPMC6690755 | biostudies-literature

KMT2D suppresses Sonic hedgehog-driven medulloblastoma progression and metastasis.

Project description:The major cause of treatment failure and mortality among medulloblastoma patients is metastasis intracranially or along the spinal cord. The molecular mechanisms driving tumor metastasis in Sonic hedgehog-driven medulloblastoma (SHH-MB) patients, however, remain largely unknown. In this study we define a tumor suppressive role of KMT2D (MLL2), a gene frequently mutated in the most metastatic β-subtype. Strikingly, genetic mouse models of SHH-MB demonstrate that heterozygous loss of Kmt2d in conjunction with activation of the SHH pathway causes highly penetrant disease with decreased survival, increased hindbrain invasion and spinal cord metastasis. Loss of Kmt2d attenuates neural differentiation and shifts the transcriptional/chromatin landscape of primary and metastatic tumors toward a decrease in differentiation genes and tumor suppressors and an increase in genes/pathways implicated in advanced stage cancer and metastasis (TGFβ, Notch, Atoh1, Sox2, and Myc). Thus, secondary heterozygous KMT2D mutations likely have prognostic value for identifying SHH-MB patients prone to develop metastasis.

| S-EPMC10562805 | biostudies-literature

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