Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide maps of H3K9me3 in hematopoietic stem cells from Kdm4a, b, c triple knockout mice

ABSTRACT: The KDM4/JMJD2 are H3K9- and H3K36- specific demethylases, which are considered promising therapeutic targets for the treatment of acute myeloid leukemia (AML) harboring MLL-translocations. Here, we investigate the long-term effects of depleting KDM4 activity on normal hematopoiesis to probe potential side effects of continuous inhibition of these enzymes. Utilizing conditional Kdm4a/Kdm4b/Kdm4c triple-knockout mice we show that KDM4 activity is required for hematopoietic stem cell (HSC) maintenance in vivo. The knockout of the KDM4 demethylases leads to accumulation of H3K9me3 on transcription start sites and the corresponding downregulation of expression of several genes in hematopoietic stem cells. We show that two of these genes, Taf1b and Nom1, are essential for the maintenance of hematopoietic cells. Taken together, our results show that the KDM4 demethylases are required for the expression of genes essential for the long-term maintenance of normal hematopoiesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE129156 | GEO | 2019/04/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

RNA-seq using RNA from KDM4 WT and Knockout haematopoietic stem cells

Project description:The KDM4/JMJD2 are H3K9- and H3K36- specific demethylases, which are considered promising therapeutic targets for the treatment of acute myeloid leukemia (AML) harboring MLL-translocations. Here, we investigate the long-term effects of depleting KDM4 activity on normal hematopoiesis to probe potential side effects of continuous inhibition of these enzymes. Utilizing conditional Kdm4a/Kdm4b/Kdm4c triple-knockout mice we show that KDM4 activity is required for hematopoietic stem cell (HSC) maintenance in vivo. The knockout of the KDM4 demethylases leads to accumulation of H3K9me3 on transcription start sites and the corresponding downregulation of expression of several genes in hematopoietic stem cells. We show that two of these genes, Taf1b and Nom1, are essential for the maintenance of hematopoietic cells. Taken together, our results show that the KDM4 demethylases are required for the expression of genes essential for the long-term maintenance of normal hematopoiesis.

2019-04-02 | GSE129137 | GEO

Jmjd2a and Jmjd2c regulate H3K9me3 and H3K36me3 at H3K4me3 positive transcription start sites being essential for ESC self-renewal and embryogenesis (ChIP-Seq)

Project description:We have characterized the role of the Jmjd2/Kdm4 proteins in embryonic stem cell (ESC) biology, histone methylation and gene regulation. The Jmjd2 proteins are H3K9/H3K36 histone demethylases and three Jmjd2 family members are expressed in ESCs: Jmjd2a/Kdm4a, Jmjd2b/Kdm4b and Jmjd2c/Kdm4c/Gasc1. We find that specifically Jmjd2a and Jmjd2c exert redundant functions, which are essential for ESC self-renewal and early embryonic development. ChIP-seq studies show that Jmjd2a and Jmjd2c both localize to H3K4me3 marked regions, where they have general and widespread roles preventing the accumulation of especially H3K9me3, but also H3K36me3. Jmjd2 catalytic activity is required for ESC maintenance, and increased H3K9me3 levels in knockout ESCs compromise the expression of several Jmjd2a/c targets, including genes that are important for ESC self-renewal. Thus, continual removal of H3K9 promoter methylation by Jmjd2 demethylases represents a novel mechanism ensuring transcriptional competence and stability of the pluripotent cell identity.

2016-05-09 | GSE64252 | GEO

Jmjd2a and Jmjd2c regulate H3K9me3 and H3K36me3 at H3K4me3 positive TSSs being essential for ESC self-renewal and embryogenesis (microarray)

2016-05-09 | GSE64251 | GEO

The KDM4/JMJD2 histone demethylases are required for hematopoietic stem cell maintenance

Project description:The KDM4/JMJD2 histone demethylases are required for hematopoietic stem cell maintenance

| PRJNA530243 | ENA

Expression landscape of human stromal cells in preclinical trials involving chemotherapeutic and histone demethylase KDM4-targeting agents

Project description:Aging and age-related pathologies including multiple cancer types can be controlled by specifically targeting senescent cells, or more specifically, their hallmark feature, the senescence-associated secretory phenotype (SASP). Lysine methylation is one of the most common histone posttranslational modifications that regulate chromatin structure in mammalian cells. Changes in histone lysine methylation status have been observed during cancer progression, a consequence of dysregulation of histone lysine methyltransferases and/or their opposing demethylases. KDM4 (or JMJD2) encompasses demethylases that target histone H3 on lysines 9 and 36 sites. Frequently overexpressed in breast, colorectal, lung, prostate, and other tumor types and required for efficient cancer cell proliferation, KDM4 proteins represent novel drug targets. However, emerging studies are beginning to uncover the functional roles of KDM4 in epigenomic regulation during cellular senescence and organismal aging, thus providing a new angle to understand human aging and allowing expansion of the existing list of epigenetic targets, the drugs of which are currently limited to the pharmacological arsenal against DNA methyltransferases and histone deacetylases.

2021-03-23 | GSE160091 | GEO

Gene regulation by the lysine demethylase KDM4A in Drosophila

Project description:Lysine methylation of histones is associated with both transcriptionally active chromatin and with silent chromatin, depending on what residue is modified. Histone methyltransferases and demethylases ensure that histone methylations are dynamic and can vary depending on cell cycle- or developmental stage. KDM4A demethylates H3K36me3, a modification enriched in the 3’end of active genes. The genomic targets and the role of KDM4 proteins in development remain largely unknown. To investigate the link between dKDM4A and transcription, and to unravel molecular targets on a genome-wide scale, we used microarrays to decipher gene expression changes in dKDM4A mutant 1st instar larvae and identified classes of up-regulated and down-regulated genes. Three replicates of 200 dKDM4A KG04636 / ∆dKDM4A and dKDM4A precise KG06436 / dKDM4A precise NP0618 Drosophila 1st instar larvae for RNA extraction and hybridization on Affymetrix microarrays.

2013-04-01 | E-GEOD-36903 | biostudies-arrayexpress

Gene regulation by the lysine demethylase KDM4A in Drosophila

2013-04-01 | GSE36903 | GEO

Efficient Elimination of Acute Myeloid Leukaemia Cells through Inhibition of KDM4A

Project description:We previously identified an essential role for the H3K9me3 histone demethylase, KDM4A, in maintaining AML cell survival, with genetic depletion by shRNA of KDM4A inducing leukaemic cell death with little effect on normal haematopoiesis. We hypothesised KDM4A inhibition may represent a novel and effective strategy to treat AML. To address this, we provided proof-of-principle for the use of KDM4 inhibitors (KDM4Ai) and fully characterised their functional potential in AML cells and identified the epigenetic mechanisms underpinning the essential role of KDM4A activity in THP-1 cells using both ChIP-seq and RNA-seq, delineating and functionally validating the epigenomic network regulated by KDM4A, showing that selective loss of KDM4A is sufficient to induce apoptosis in a broad spectrum of human AML cells. This detrimental phenotype results from a global accumulation of H3K9me3 and H3K27me3 at KDM4A targeted genomic loci thereby causing down-regulation of a KDM4A-PAF1 controlled transcriptional program essential for leukemogenesis, distinct from that of KDM4C.

2022-12-31 | GSE173995 | GEO

Early B Cell Factor 2 Regulates Hematopoietic Stem Cell Homeostasis in a Cell-Nonautonomous Manner

Project description:Hematopoiesis requires the interaction of hematopoietic stem cells (HSCs) with various stromal microenvironments. Here, we examine the role of early B cell factor 2 (Ebf2), a transcription factor expressed in a subset of immature osteoblastic cells. Ebf2-/- mice show decreased frequencies of HSCs and lineage-committed progenitors. This defect is cell nonautonomous, as shown by the fact that transplantation of Ebf2-deficient bone marrow into wild-type hosts results in normal hematopoiesis. In coculture experiments, Ebf2 Ebf2-/-osteoblastic cells have reduced potential to support short-term proliferation of HSCs. Expression profiling of sorted Ebf2-/- osteoblastic cells indicated that several genes implicated in the maintenance of HSCs are downregulated relative to Ebf2+/- cells, whereas genes encoding secreted frizzled-related proteins are upregulated. Moreover, HSCs from Ebf2-/- mice and wild-type HSCs cocultured with Ebf2-/- osteoblastic cells show reduced Wnt responses. Thus, Ebf2 acts as a transcriptional determinant of an osteoblastic niche that regulates the maintenance of hematopoietic progenitors, in part by modulating Wnt signaling.

2011-04-26 | GSE21700 | GEO

The CKS1/CKS2 proteostasis axis is crucial to maintain hematopoietic stem cell function

Project description:Long-term hematopoietic stem cells are rare, highly quiescent stem cells of the hematopoietic system with life-long self-renewal potential and the ability to transplant and reconstitute the entire hematopoietic system of conditioned recipients. Most of our understanding of these rare cells has relied on cell surface identification, epigenetic and transcriptomic analyses. Our knowledge of protein synthesis, folding, modification and degradation – broadly termed protein homeostasis or “proteostasis” – in these cells is still in its infancy. Here we report the requirement of the small phospho-binding adaptor proteins, the cyclin dependent kinase subunits (Cks1 and Cks2), for maintaining ordered hematopoiesis and long-term hematopoietic stem cell reconstitution. Cks1 and Cks2 are critical regulators of a myriad of key intracellular signalling pathways that govern hematopoietic stem cell biology and together they balance protein homeostasis and restrain reactive oxygen species to ensure healthy hematopoietic stem cell function.

2023-03-11 | PXD035984 | Pride

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