The histone demethylase JMJD1A is essential to prostate cancer cells through regulation of c-Myc expression
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE70498 | GEO | 2015/09/08
SECONDARY ACCESSION(S): PRJNA288819
REPOSITORIES: GEO
Similar Datasets
Project description:Analysis of gene expresssion altered upon knockdown of histone demethylase JMJD1A in human prostate cancer cells. The objective is to elucidate the transcriptional programs that are controlled by JMJD1A in human prostate cancer. CWR22Rv1 prostate cancer cells were transduced with lentiviral particles encoding control pLKO.1 or JMJD1A shRNA (shJMJD1A). After 48 h, total RNAs were collected for the microarray analysis to determine the differentially expressed genes between Rv1 pLKO.1 and Rv1 shJMJD1A samples.
2015-09-08 | E-GEOD-70498 | biostudies-arrayexpress
Project description:Developmental gene expression is defined through cross-talk between the function of transcription factors and epigenetic status including histone modification. Although several known transcription factors play crucial roles in mammalian sex determination, how chromatin regulation contributes to this process is unknown. We observed male-to-female sex reversal in mice lacking the H3K9 demethylase Jmjd1a, and found that Jmjd1a directly regulates expression of the mammalian Y chromosome sex-determining gene Sry, by regulating H3K9me2 marks. These studies reveal a pivotal role for epigenetic regulation in mammalian sex determination, and provide new impetus for identifying additional causes of disorders of sex determination by environmental factors. Gene expression patterns were measured in gonadal somatic cells of Jmjd1a mutant and control embryos at E11.5. Three biological replicates were performed in each group.
2013-08-03 | E-GEOD-49513 | biostudies-arrayexpress
Project description:The histone demethylase JMJD1A（Jumoji domain containing 1A） is overexpressed in multiple cancers and promotes cancer progression. However, the role and mechanism of JMJD1A in gastric cancer remains poorly understood.Here, we found that JMJD1A could suppress gastric cancer cell proliferation, migration, invasion and xenograft tumor growth. Using RNA sequencing, we identified RUNX3 as a novel target gene of JMJD1A.
2020-02-12 | GSE145105 | GEO
Project description:Developmental gene expression is defined through cross-talk between the function of transcription factors and epigenetic status including histone modification. Although several known transcription factors play crucial roles in mammalian sex determination, how chromatin regulation contributes to this process is unknown. We observed male-to-female sex reversal in mice lacking the H3K9 demethylase Jmjd1a, and found that Jmjd1a directly regulates expression of the mammalian Y chromosome sex-determining gene Sry, by regulating H3K9me2 marks. These studies reveal a pivotal role for epigenetic regulation in mammalian sex determination, and provide new impetus for identifying additional causes of disorders of sex determination by environmental factors.
2013-08-03 | GSE49513 | GEO
Project description:The Hypoxia-Inducible Factors induce the expression of the histone demethylases JMJD1A (KDM3A) and JMJD2B (KDM4B), linking the hypoxic tumor microenvironment to epigenetic mechanisms that may foster tumor progression. Using transcript profiling, we have identified genes that are regulated by JMJD1A and JMJD2B in both normoxic and hypoxic conditions in SKOV3ip.1 ovarian cancer cells. This dataset includes expression data obtained from exposing ovarian cancer cells to hypoxia in combination with siRNA-mediated knockdown of the hypoxia-inducible histone demethylases JMJD1A and JMJD2B. These data were used to both identify functional overlap between each histone demethylase, as well as identify effectors of tumor growth mediated by JMJD2B (KDM4B) in normoxia and hypoxia.
2017-03-13 | GSE66894 | GEO
Project description:Histone H3 lysine 9 (H3K9) methylation is an epigenetic mark of transcriptionally repressed chromatin. During mammalian development, H3K9 methylation levels seem to be spatiotemporally regulated by the opposing activities of methyltransferases and demethylases to govern correct gene expression. However, the combination(s) of H3K9 methyltransferase(s) and demethylase(s) that contribute to this regulation and the genes regulated by them remain unclear. Herein, we demonstrate the essential roles of H3K9 demethylases Jmjd1a and Jmjd1b in the embryogenesis and viability control of embryonic stem (ES) cells. Mouse embryos lacking Jmjd1a/Jmjd1b died after implantation. Depletion of Jmjd1a/Jmjd1b in mouse ES cells induced rapid cell death accompanied with a massive increase in H3K9 methylation. Jmjd1a/Jmjd1b depletion induced an increase in H3K9 methylation in the gene-rich regions of the chromosomes, indicating that Jmjd1a/Jmjd1b removes H3K9 methylation marks in the euchromatin. Importantly, the additional disruption of the H3K9 methyltransferase G9a in a Jmjd1a/Jmjd1b-deficient background rescued not only the H3K9 hypermethylation phenotype but also the cell death phenotype. We also found that Jmjd1a/Jmjd1b removes H3K9 methylation marks deposited by G9a in the Oct4 and Ccnd1 loci to activate transcription. In conclusion, Jmjd1a/Jmjd1b ensures ES cell viability by antagonizing G9a-mediated H3K9 hypermethylation in the gene-rich euchromatin.
2018-03-14 | GSE98761 | GEO
Project description:Matrix induced effects on gene expression in HeLa and MDA-MB-231 cells Tissue homeostasis is dependent on the spatially controlled localization of specific cell types and the correct composition of the extracellular stroma. While the role of the cancer stroma in tumor progression has been well characterized, the specific contribution of the matrix itself is unknown. Furthermore, the mechanisms enabling normal – not cancer – stroma to provide tumor suppressive signals and act as an anti-tumorigenic barrier are poorly understood. Here, we show that extracellular matrix (ECM) generated by normal fibroblasts (NFs) is softer than CAF-matrix and it is the physical and structural features of NF-generated matrix that regulate cancer cell proliferation . We find that normal stromal ECM triggers downregulation and nuclear exit of the histone demethylase JMJD1a resulting in the epigenetic growth restriction of carcinoma cells. Interestingly, JMJD1a positively regulates transcription of many target genes, including YAP/TAZ, and thus therefore gene expression in stiffness-dependent manner. Thus normal stromal restricts cancer cell proliferation through JMJD1a-dependent modulation of gene expression.
2016-08-29 | GSE83366 | GEO
Project description:Mitochondria play a vital role in non-shivering thermogenesis in both brown and subcutaneous white adipose tissues (BAT and scWAT, respectively). However, specific regulatory mechanisms driving mitochondrial function in these tissues have been unclear. Here we demonstrate that prolonged activation of β-adrenergic signaling induces epigenetic modifications in scWAT, specifically targeting the enhancers for the mitochondria master regulator genes Pgc1a/b. This is mediated at least partially through JMJD1A, a histone demethylase that in response to β-adrenergic signals, facilitates H3K9 demethylation of the Pgc1a/b enhancers, promoting mitochondrial biogenesis and the formation of beige adipocytes. Disruption of demethylation activity of JMJD1A in mice impairs activation of Pgc1a/b driven mitochondrial biogenesis and limits scWAT beiging, contributing to reduced energy expenditure, obesity, insulin resistance, and metabolic disorders. Notably, JMJD1A demethylase activity is not required for Pgc1a/b dependent thermogenic capacity of BAT especially during acute cold stress, emphasizing the importance of scWAT thermogenesis in overall energy metabolism.
2024-03-12 | GSE236733 | GEO
Project description:The current studies show that JMJD1A is phosphorylated at S265 by protein kinase A (PKA), and this is pivotal to activate expression of the b1-adrenergic receptor gene (Adrb1) and downstream targets including Ucp1. Phosphorylation of JMJD1A increases its interaction with the SWI/SNF nucleosome remodeling complex and DNA-bound PPARg. This complex conferred b-adrenergic-induced JMJD1A recruitment to target sites throughout the genome. Phospho-JMJD1A also facilitated long-range chromatin looping to recruit PPARg-bound distal-enhancers, SWI/SNF, and RNA polymerase close to the Adrb1 locus to activate transcription. Mutation of the PKA-phosphorylation site on JMJD1A abolished interactions with SWI/SNF without affecting demethylase activity suggesting the two functions are independent of each other. Our results show that JMJD1A demethylase is also a signal-sensing scaffold that regulates cAMP-responsive transcription via interactions with SWI/SNF and hormone stimulated higher-order chromatin conformational changes. There are 3 samples analyzed. No duplication from each sample. Isoproterenol stimulation at 0hr is used as the relative to fold change in manuscript.
2015-04-15 | E-GEOD-58936 | biostudies-arrayexpress
Project description:The histone demethylase JMJD1A, which controls gene expression by epigenetic regulation of H3K9 methylation marks, functions in diverse activities, including spermatogenesis, metabolism and stem cell self-renewal and differentiation. Here, we found that JMJD1A knockdown in prostate cancer cells antagonizes their proliferation and survival. Profiling array analyses revealed that JMJD1A-dependent genes function in cellular growth, proliferation and survival, and implicated that the c-Myc transcriptional network is deregulated following JMJD1A inhibition. Biochemical analyses confirmed that JMJD1A enhances c-Myc transcriptional activity by upregulating c-Myc expression levels. Mechanistically, JMJD1A activity promoted recruitment of androgen receptor (AR) to the c-Myc gene enhancer and induced H3K9 demethylation, increasing AR-dependent transcription of c-Myc mRNA. In parallel, we found that JMJD1A regulated c-Myc stability, likely by inhibiting HUWE1, an E3 ubiquitin ligase known to target degradation of several substrates including c-Myc. JMJD1A (wild type or mutant lacking histone demethylase activity) bound to HUWE1, attenuated HUWE1-dependent ubiquitination and subsequent degradation of c-Myc, increasing c-Myc protein levels. Furthermore, c-Myc knockdown in prostate cancer cells phenocopied effects of JMJD1A knockdown, and c-Myc re-expression in JMJD1A-knockdown cells partially rescued prostate cancer cell growth in vitro and in vivo. c-Myc protein levels were positively correlated with those of JMJD1A in a subset of human prostate cancer specimens. Collectively, our findings identify a critical role for JMJD1A in regulating proliferation and survival of prostate cancer cells by controlling c-Myc expression at transcriptional and post-translational levels.
| S-EPMC4757517 | biostudies-other