Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA297699 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR2551244_1.fastq.gz | Fastqsanger.gz | |||
| SRR2551244_2.fastq.gz | Fastqsanger.gz | |||
| SRR2551245_1.fastq.gz | Fastqsanger.gz | |||
| SRR2551245_2.fastq.gz | Fastqsanger.gz | |||
| SRR2551246_1.fastq.gz | Fastqsanger.gz |
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Project description:Mutations in the JMJD3 (KDM6B) chromatin regulator are causally associated with autism spectrum disorder and syndromic intellectual disability, but the neurodevelopmental roles of this histone 3 lysine 27 (H3K27) demethylase are poorly understood. Neural stem cells (NSCs) in the hippocampal dentate gyrus (DG) generate new granule neurons throughout life, and deficits in DG neurogenesis are associated with cognitive and behavioral problems. Here we show that Jmjd3 is required for the establishment of adult neurogenesis in the mouse DG. Conditional deletion of Jmjd3 in embryonic DG precursors results in an adult hippocampus that is essentially devoid of NSCs. While early postnatal mice with Jmjd3-deletion have near normal numbers of DG NSCs, at later stages, Jmjd3-deleted NSCs fail to propagate normally. In addition to the loss of NSCs during postnatal development, neurogenesis from Jmjd3-deleted NSCs is impaired, corresponding to defective neurogenic gene expression. Without Jmjd3, NeuroD2 and Bcl11b(Ctip2) are not properly expressed and exhibit increased levels of H3K27me3, underscoring the role of Jmjd3 in the regulation of transcription for neuronal differentiation. Thus, these data indicate that Jmjd3 plays dual roles in postnatal DG neurogenesis, being critical for the establishment of the NSC pool as well as the differentiation of young DG granule neurons. More broadly, our results suggest a neurodevelopmental link between JMJD3 mutations and hippocampal dysfunction, providing new insights into how mutations in chromatin regulators may contribute to learning disorders.
2021-04-01 | GSE73706 | GEO
Project description:The epigenetic mechanisms that enable lifelong neurogenesis from neural stem cells (NSCs) in the adult mammalian brain are poorly understood. Here we show that JMJD3, a histone H3-lysine 27 (H3K27) demethylase, acts as a critical activator of neurogenesis. 3 biological replicates of JMJD3 null (P9 UBC-Cre/ERT2;Jmjd3F/F) and 3 biological replicates of littermate controls were used to analyze the effect of JMJD3 deletion on gene expression.
2014-07-30 | E-GEOD-59888 | biostudies-arrayexpress
Project description:The epigenetic mechanisms that enable lifelong neurogenesis from neural stem cells (NSCs) in the adult mammalian brain are poorly understood. Here we show that JMJD3, a histone H3-lysine 27 (H3K27) demethylase, acts as a critical activator of neurogenesis.
2014-07-30 | GSE59888 | GEO
Project description:Autophagy is essential for cellular survival and energy homeostasis under nutrient deprivation. Despite the emerging importance of nuclear events in autophagy regulation, epigenetic control of autophagy gene transcription remains unclear. Here, we identify Jumonji-D3 (JMJD3/KDM6B) histone demethylase as a key epigenetic activator of hepatic autophagy. Upon fasting-induced fibroblast growth factor-21 (FGF21) signaling, JMJD3 epigenetically upregulated global autophagy-network genes, including Tfeb, Atg7, Atgl, and Fgf21, through demethylation of histone H3K27-me3, resulting in autophagy-mediated lipid degradation. Mechanistically, phosphorylation of JMJD3 at Thr-1044 by FGF21 signal-activated PKA increased its nuclear localization and interaction with the nuclear receptor PPARto transcriptionally activate autophagy. Chronic administration of FGF21 in obese mice improved defective autophagy and hepatosteatosis in a JMJD3-dependent manner. Remarkably, in non-alcoholic fatty liver disease patients, hepatic expression of JMJD3, ATG7, LC3, and KL were substantially decreased. These findings demonstrate that FGF21-JMJD3 signaling epigenetically links nutrient deprivation with hepatic autophagy and lipid degradation in mammals
2020-05-26 | PXD015672 | Pride
Project description:The histone lysine demethylase Kdm6b is required for activity-dependent preconditioning of hippocampal neuronal survival
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Project description:Recent studies have delineated cancer type-specific roles of histone 3 lysine 27 (H3K27) demethylase KDM6B/JMJD3 depending on its H3K27 demethylase activity. Here we show that KDM6B is expressed in multiple myeloma (MM); and that shRNA-mediated knockdown and CRISPR-mediated knockout of KDM6B abrogate MM cell growth and survival. TNFα or bone marrow stromal cell culture supernatants induce KDM6B, which is blocked by IKKβ inhibitor MLN120B, suggesting KDM6B is regulated by NF-κB signaling in MM cells. RNA-sequencing and subsequent ChIP-qPCR analyses reveal that KDM6B is recruited to the loci of genes encoding components of MAPK signaling pathway including ELK1 and FOS, and upregulates these genes expression without affecting H3K27 methylation level. Overexpression of catalytically-inactive KDM6B activates expression of MAPK pathway-related genes, confirming its function independent of demethylase activity. We further demonstrate that downstream targets of KDM6B, ELK1 and FOS, confer MM cell growth. Our study therefore delineates KDM6B function that links NF-κB and MAPK signaling pathway mediating MM cell growth and survival, and validates KDM6B as a novel therapeutic target in MM.
2017-05-01 | GSE93395 | GEO
Project description:Neural development requires crosstalk between signaling pathways and chromatin. In this study, we demonstrate that neurogenesis is promoted by an interplay between the TGFM-NM-2 pathway and the H3K27me3 histone demethylase (HDM) JMJD3. Genome-wide analysis showed that JMJD3 is targeted to gene promoters by Smad3 in neural stem cells (NSCs) and is essential to activate TGFM-NM-2-responsive genes. In vivo experiments in chick spinal cord revealed that the generation of neurons promoted by Smad3 is dependent on JMJD3 HDM activity. Overall, these findings indicate that JMJD3 function is required for the TGFM-NM-2 developmental program to proceed. We immunoprecipitate endogenous Smad3 or JMJD3 proteins from neural stem cells treated with TGFb for 30 minutes.
2012-05-30 | E-GEOD-36673 | biostudies-arrayexpress
Project description:The discovery of the first histone demethylase in 2004 (LSD1/KDM1) opened new avenues for the understanding of how histone methylation impacts cellular functions. A great number of histone demethylases have been identified since, which are potentially linked to gene regulation as well as to stem cell self-renewal and differentiation. KDM6A/UTY and KDM6B/JMJD3 are both H3K27me3/2-specific histone demethylases, which are known to play a central role in regulation of posterior development, by regulating HOX gene expression. So far nothing is known about the role of histone lysine demethylases (KDMs) during early hematopoiesis. We are studying the role of KDM6A and KDM6B on self-renewal, global gene expression and on local and global chromatin states in embryonic stem cells (ESCs) and during differentiation. In order to completely abrogate KDM6 demethylase activity in ESCs we employed a specific inhibitor (GSK-J4, Kruidenier et al. 2012). Treatment of ESCs with GSK-J4 had no effect on viability and proliferation . However, ESC differentiation in the presence of GSK-J4 was completely abrogated. In conclusion we show that ESC differentiation is completely blockend in the absence of any H3K27 demethylase activity. We used microarrays to detail the global gene expression program of genes which are differentially expressed during the early differentiation of ESC derived embryoid bodies (EBs) in the presence of GSK-J4 (KDM6 Inhibitor). ESCs (R1) have been cultured and differentiated in the presence of GSK-J4 a KDM6 specific inhibitor.
2016-03-11 | E-GEOD-49886 | biostudies-arrayexpress
Project description:Recent studies have indicated that the histone 3 lysine 27 (H3K27me2/3) demethylase KDM6B (JMJD3) is frequently upregulated in a myriad of blood disorders including myelodysplastic syndrome (MDS), T-cell acute lymphoblastic leukemia (T-ALL), and multiple myeloma (MM) suggesting it may have important functions in the pathogenesis of hematopoietic cancers. Here, we sought to determine the role of Kdm6b in hematopoietic stem cell (HSC) fate decisions under normal and malignant conditions to evaluate its potential as a therapeutic target. We show that loss of Kdm6b leads to a significant reduction in phenotypic and functional HSCs in adult mice, and that Kdm6b is necessary for HSC self-renewal in response to inflammatory, genotoxic and oncogenic stress. Additionally, we show that loss of Kdm6b in HSCs leads to a stress-response gene expression signature in native HSCs that is independent of its demethylase activity. Loss of Kdm6b lead to increased expression of a subset of genes implicated in HSC quiescence (e.g. Fos, Jun, Ier2, Dusp1, Zfp36). Upon inflammatory or replicative stress, HSCs deficient for Kdm6b are not able to efficiently resolve this gene expression program, leading to increased quiescence and a self-renewal block, forcing them to differentiate. These findings show that Kdm6b is necessary for self-renewal of normal and leukemic stem cells, and suggest inhibiting Kdm6b in blood cancers in the presence of proliferative agents may force differentiation and eventual depletion of leukemic stem cells.
2019-07-17 | GSE110378 | GEO
Project description:Neural development requires crosstalk between signaling pathways and chromatin. In this study, we demonstrate that neurogenesis is promoted by an interplay between the TGFM-NM-2 pathway and the H3K27me3 histone demethylase (HDM) JMJD3. Genome-wide analysis showed that JMJD3 is targeted to gene promoters by Smad3 in neural stem cells (NSCs) and is essential to activate TGFM-NM-2-responsive genes. In vivo experiments in chick spinal cord revealed that the generation of neurons promoted by Smad3 is dependent on JMJD3 HDM activity. Overall, these findings indicate that JMJD3 function is required for the TGFM-NM-2 developmental program to proceed Mouse neural stem cells (NSC) control and JMJD3 knock down (shctrl and shJMJD3) were treated with the vehicle (-TGFb) or TGFbeta 5ng/ml (+TGFb) for 2.5h. Three replicates were performed for each point. And all of them were use it to posterior analysis.
2012-04-30 | E-GEOD-35361 | biostudies-arrayexpress