Histone demethylase JMJD3 disrupts spectrin-dependent cytoskeleton via activation of HKDC1 to suppress Pancreatic Ductal Adenocarcinoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE85933 | GEO | 2017/05/01
SECONDARY ACCESSION(S): PRJNA339782
REPOSITORIES: GEO
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Project description:Purpose:To indentify downtream effectors of JMJD3, we performed microarray profiling in vector- or JMJD3-expressing A375-LM3 and those in freshly isolated melanoma cells from tumors formed by aforementioned cell lines Results: we identifed 31 genes whose expression increased in WT JMJD3 expression cells at least by over 1.5-fold.
2016-02-03 | GSE72289 | 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:Next Generation Sequencing Facilitates Quantitative Analysis of HL-60 cells transduced with control or JMJD3-expression vector, and HL-60 parental and JMJD3 knockout cells
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Project description:ChIP seq of endogenous Smad3 and JMJD3 proteins in mouse embryonic neural stem cells treated with TGFbeta during 30 minutes. Neural stem cells were treated with TGFbeta during 30 minutes, and then chromatin immunoprecipitation was carried out with specific JMJD3 or Smad3 antibodies. Positive and negative controls for each immunoprecipitation were checked before sequencing. Input was used to normalized the sequencing results.
2011-12-30 | E-MTAB-825 | biostudies-arrayexpress
Project description:Gene expression profiles were compared between wild-type and Jmjd3-/- embryos at E9.5 when mRNAs of posterior Hox genes are upregulated, because Jmjd3-/- mice embryos showed homeotic transformation. As expected, mRNAs of Hoxd10 and Hod11 were decreased in Jmjd3-/- embryos. Moreover, gene onthology (GO) analyses identified down-regulated genes (FC>1.5) in Jmjd3-/- embryos were M-bM-^@M-^\multicellular organismal developmentM-bM-^@M-^] and M-bM-^@M-^\developmental processM-bM-^@M-^]. Gene expressions in wild-type and Jmjd3-/- posterior half of embryos at E9.5 were examined. Two independent RNA samples of each genotypes were used to verify the reproducibility of the microarray analyses.
2014-02-23 | E-GEOD-40332 | biostudies-arrayexpress
Project description:Several signaling pathways require JMJD3 binding to promoters to activate the expression of target genes. Despite the known H3K27me3 demethylase activity of JMJD3 the transcriptional coactivator mechanism remains unclear. Here we reveal that JMJD3 promotes transcription of TGFb responsive genes through regulation of RNAPII progression on gene bodies. ChIPseq experiments demonstrate that upon TGFb treatment, JMJD3 and RNAPII.ser2P colocalyze extensively along intragenic regions of TGF target genes. M-BM- According to these data, genome wide analysis shows that JMJD3 dependent TGF target genes are enriched in H3K27me3 prior to TGF signaling pathway activation. M-BM- Further molecular analysis indicate that JMJD3 removes H3K27me3 and pave the way for the RNAPII.Overall, these findingsM-BM- uncover the mechanism ofM-BM- JMJD3 function in transcriptional activation We performed chromatin immunoprecipitation followed by sequencing (ChIPseq) of H3K27me3 mark in mouse neural stem cells growing under standard conditions. We also performed ChIPseq of elongating RNAPII (Ser2P) and JMJD3 in neural stem cells stimulated with TGFb cytokine.
2012-12-31 | E-GEOD-38269 | biostudies-arrayexpress
Project description:Next Generation Sequencing Facilitates Quantitative Analysis of NB4 cells transduced with control or JMJD3-expression vector. JMJD3, a stress-inducible H3K27 demethylase, plays a critical regulatory role in the initiation and progression of malignant hematopoiesis. However, how this histone modifier effects in a cell type-dependent manner remains unclear. Here, we show that in contrast to its oncogenic effect in preleukemia state and lymphoid malignancies, JMJD3 relieves the differentiation-arrest of certain subtypes (such as M2 and M3) of acute myeloid leukemia (AML) cells. RNA-sequencing and ChIP-PCR analyses revealed that JMJD3 exerts anti-AML effect by directly modulating H3K4 and H3K27 methylation levels to activate the expression of a number of key myelopoietic regulatory genes. Mechanistic exploration identified a physical and functional association of JMJD3 with C/EBPb that presides the regulatory network of JMJD3. Thus, the leukemia regulatory role of JMJD3 varies in a disease phase- and lineage-dependent manner, and acts as a potential oncorepressor in certain subsets of AML largely by coupling to C/EBPb-centered myelopoietic program.
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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
Project description:Gene expression profiles were compared between wild-type and Jmjd3-/- embryos at E9.5 when mRNAs of posterior Hox genes are upregulated, because Jmjd3-/- mice embryos showed homeotic transformation. As expected, mRNAs of Hoxd10 and Hod11 were decreased in Jmjd3-/- embryos. Moreover, gene onthology (GO) analyses identified down-regulated genes (FC>1.5) in Jmjd3-/- embryos were “multicellular organismal development” and “developmental process”.
2014-02-23 | GSE40332 | GEO