Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The histone demethylase KDM3A regulates the transcriptional program of the androgen receptor in prostate cancer cells

ABSTRACT: The lysine demethylase 3A (KDM3A, JMJD1A or JHDM2A) controls transcriptional networks in a variety of biological processes such as spermatogenesis, metabolism, stem cell activity and tumor progression. We matched transcriptomic and ChIP-Seq profiles to decipher a genome-wide regulatory network of epigenetic control by KDM3A in prostate cancer cells. ChIP-Seq experiments monitoring histone 3 lysine 9 (H3K9) methylation marks show global histone demethylation effects of KDM3A. Combined assessment of histone demethylation events and gene expression changes presented major transcriptional activation suggesting that distinct oncogenic regulators may synergize with the epigenetic patterns by KDM3A. Pathway enrichment analysis of cells with KDM3A knockdown prioritized androgen signaling indicating that KDM3A plays a key role in regulating androgen receptor activity. Matched ChIP-Seq and knockdown experiments of KDM3A in combination with ChIP-Seq of the androgen receptor resulted in a gain of H3K9 methylation marks around androgen receptor binding sites of selected transcriptional targets in androgen signaling including positive regulation of KRT19, NKX3-1, KLK3, NDRG1, MAF, CREB3L4, MYC, INPP4B, PTK2B, MAPK1, MAP2K1, IGF1, E2F1, HSP90AA1, HIF1A, and ACSL3. The cancer systems biology analysis of KDM3A-dependent genes identifies an epigenetic and transcriptional network in androgen response, hypoxia, glycolysis, and lipid metabolism. Genome-wide ChIP-Seq data highlights specific gene targets and the ability of KDM3A to control oncogenic pathways in prostate cancer cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE109748 | GEO | 2019/05/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Critical roles of lysine demethylase Kdm3a in craniofacial and neural development during Xenopus embryogenesis

Project description:The epigenetic modifier lysine-specific histone demethylase 3a (kdm3a) is specific for demethylation of mono- and di-methylated 9th lysine of histone H3 (H3K9me1/2) and belongs to the Jumonji domain-containing group of demethylases. Kdm3a is known to play significant roles during various biological and pathophysiological processes such as spermatogenesis and metabolism, determination of sex, androgen receptor-mediated transcription, and embryonic carcinoma cell differentiation. In the current study, we evaluated the physiological functions of kdm3a during Xenopus laevis embryogenesis. Spatiotemporal expression pattern indicated maternal nature of kdm3a, exhibiting its expression from early embryonic stages until tadpole stage, however considerable high level of expression were observed during the neurula stage of Xenopus development. Depleting kdm3a using kdm3a antisense morpholino oligonucleotides induced anomalies, such as head deformities and small-sized eyes. Our whole-mount in situ hybridization results demonstrated that kdm3a knockdown is associated with defects in neural crest formation and migration. Further, reverse transcription polymerase chain reaction revealed abnormal expression of neural markers in kdm3a morphants. RNA sequencing of kdm3a morphants indicated that kdm3a is implicated in mesoderm formation, cell adhesion, and metabolic processes of embryonic development. In conclusion, we suggest that kdm3a is critical for neural development during Xenopus embryogenesis and can be targeted for treatment of developmental disorders. The further detailed investigation is required to understand the molecular mechanism involved in neural development regulation by kdm3a.

2018-11-23 | GSE117754 | GEO

β-adrenergic signaling-regulated MYPT1-PP1β phosphatase bridges chromatin states and actomyosin-tension-mediated YAP/TAZ transcriptional network for beige adipogenesis under cold stress

Project description:Protein kinase A phosphorylates proteins including histone H3 lysine 9 (H3K9) demethylase JMJD1A to facilitate beige adipogenesis upon β-adrenergic receptor (β-AR) activation, however, phosphatase(s) that antagonizes phosphorylation to inhibit beige adipogenesis is incompletely understood. Here we show that MYPT1-PP1β is a phosphatase that negatively regulates beige adipogenesis via dephosphorylation of pS265-JMJD1A and myosin regulatory light chain. Upon β-AR activation, MYPT1-PP1β is inhibited via T694 phosphorylation of MYPT1, facilitating phosphorylation of JMJD1A and beige adipogenesis under cold stress. Depletion of MYPT1-PP1β induces Ucp1 by orchestrating JMJD1A-mediated H3K9 demethylation and actomyosin-tension mediated YAP/TAZ activation. This induction of Ucp1 is abrogated in adipocytes expressing catalytically dead JMJD1A mutant, indicating that the coordinated epigenetic and transcriptional mechanisms are essential for beige adipogenesis. We also show that preadipocytes specific Mypt1 deficient mice exhibit higher cold tolerance with higher Ucp1 levels in subcutaneous white adipose tissues compared to control mice confirming its role at animal levels.

2022-09-26 | PXD031210 | JPOST Repository

Gene expression profiles of RPMI8226 cells after knockdown of KDM3A and KLF2

Project description:Recent studies have implicated KDM3A, which catalyzes removal of H3K9 methylation, is associated with tumorigenesis. However, the biological role of KDM3A in multiple myeloma, has not been delineated. Here we identify KDM3A-KLF2-IRF4 axis dependence in multiple myeloma. We demonstrate that knockdown of KDM3A leads to apoptosis and significant growth inhibition in myeloma cells. Mechanistically, KDM3A directly regulates myeloma cell survival factor IRF4 expression through H3K9 demethylation at its promoter. We further show that KDM3A directly regulates KLF2 expression and that knockdown of KLF2 leads to growth inhibition in myeloma cells. The goal of this analysis is to identify genes whose expression changes after shRNA-mediated knockdown of KDM3A and KLF2 using the human U133 plus 2.0 Affymetrix GeneChip in myeloma cell line (RPMI8226). Two independent experiments were performed: 1. Myeloma cell line (RPMI8226) was transduced with either shRNAs targeting KDM3A (duplicate hairpins) or luciferase (control) in duplicate. The gene expression profiles of KDM3A knockdown cells were compared with that of control cells. A total of 6 RNA samples (4 KDM3A knockdown and 2 control) were analyzed. 2. Myeloma cell line (RPMI8226) was transduced with either shRNAs targeting KLF2 (duplicate hairpins) or luciferase (control) in duplicate. The gene expression profiles of KLF2 knockdown cells were compared with that of control cells. A total of 6 RNA samples (4 KLF2 knockdown and 2 control) were analyzed.

2015-02-18 | E-GEOD-55667 | biostudies-arrayexpress

Gene expression profiles of RPMI8226 cells after knockdown of KDM3A and KLF2

2015-02-18 | GSE55667 | GEO

Histone Demethylase KDM3A Functions As an Essential Factor for Epigenetic Control of Autophagy

Project description:Autophagy phenomenon is an essential mechanism to regulate cell homeostasis and is activated by various stresses such as nutrient starvation. It is well known that when autophagy is activated and how important components in the cytoplasm cause a series of reactions, but the regulatory mechanism of transcription in the nucleus is poorly known. Here, we identify that histone demethylase KDM3A plays a crucial role in the transcription of autophagy and lysosomal genes. Notably, KDM3A is increased in transcriptional levels in both glucose and amino acid starvation. Especially, transcriptional increase of histone demethylase in response to glucose starvation is dependent on AMP-activated protein kinase (AMPK). Furthermore, genome-wide analysis reveals that KDM3A acts as a co-activator in the expression of autophagy and lysosomal genes. Our finding of histone demethylase signaling cascade in nucleus, modulating histone demethylation signature is one of the predominant epigenetic event in autophagy activation, thereby providing the functional and mechanistic link between epigenetic control and transcriptional regulation of autophagy upon nutrient starvation.

2020-08-30 | GSE103573 | GEO

Lysine-Specific Demethylase 1 Has Dual Functions as a Major Regulator of Androgen Receptor Transcriptional Activity

Project description:Lysine Specific Demethylase 1 (LSD1, KDM1A) functions as a transcriptional corepressor through demethylation of histone 3 lysine 4 (H3K4), but has coactivator function on some genes through unclear mechanisms. We show that LSD1, interacting with CoREST, associates with and coactivates androgen receptor (AR) on a large fraction of androgen-stimulated genes. A subset of these AR/LSD1-associated enhancer sites have histone 3 threonine 6 phosphorylation (H3T6ph), and these sites are further enriched for androgen-stimulated genes. Significantly, despite its coactivator activity, LSD1 still mediates H3K4me2 demethylation at these androgen-stimulated enhancers. FOXA1 is also associated with LSD1 at AR regulated enhancer sites, and a FOXA1 interaction with LSD1 enhances binding of both proteins at these sites. These findings show LSD1 functions broadly as a regulator of AR function, that it maintains a transcriptional repression function at AR-regulated enhancers through H3K4 demethylation, and has a distinct AR-linked coactivator function mediated by demethylation of other substrates. Determine the role of LSD1 in androgen signaling.

2014-12-12 | E-GEOD-52201 | biostudies-arrayexpress

The histone demethylase Kdm3a is essential to progression through differentiation

Project description:Histone demethylation has important roles in regulating gene expression and forms part of the epigenetic memory system that regulates cell fate and identity, by still poorly understood mechanisms. Here we examined the role played by the histone demethylase Kdm3a, which demethylates lysine 9 of histone H3, during cellular differentiation. Using F9 mouse embryonal carcinoma cells as a model for progression through terminal differentiation, we showed that Kdm3a is essential to differentiation into parietal endoderm-like (PE) cells. On gene expression microarrays, we found several genes whose expression is upregulated by Kdm3a during endoderm differentiation, including the three developmental master players Dab2, Pdlim4, and FoxQ1. The role of Kdm3a as a transcriptional activator of these genes was correlated with its effect by demethylating dimethyl-lysine 9 of histone H3 (H3K9me2) at their promoters. We further demonstrated that Dab2 depletion, like Kdm3a depletion, prevents F9 cells from fully differentiating into PE cells. Nevertheless, the only overexpression of Dab2 in Kdm3a-depleted cells is not sufficient to completely restore the PE differentiation in Kdm3a-knockdown cells. Overall, our findings reveal that Kdm3a is crucial for progression through terminal differentiation, likely by regulating the expression of a set of master players in endoderm differentiation. The emergence of Kdm3a as a key modulator of cell fate decision strengthens the notion that histone demethylases are at the nexus of cell differentiation and development.

2012-06-15 | GSE33841 | GEO

LNCaP LSD1 knockdown and SP-2509 treatment ChIP-seq data

Project description:LSD1 (also known as KDM1A) is a histone demethylase and a key regulator of gene expression in embryonic stem cells and cancer.1,2 LSD1 was initially identified as a transcriptional repressor via its demethylation of active histone H3 marks (di-methyl lysine 4 [2MK4]).1 In prostate cancer, specifically, LSD1 also co-localizes with the AR and demethylates repressive 2MK9 histone marks from androgen-responsive AR target genes, facilitating androgen-mediated induction of AR-regulated gene expression and androgen-induced proliferation in androgen-dependent cancers. We report here that the LSD1 protein is universally upregulated in human CRPC and promotes survival of CRPC cell lines. This effect is explained in part by LSD1-induced activation of cell cycle and embryonic stem cell gene setsâgene sets enriched in transcriptomal studies of lethal human tumors. Importantly, despite the fact that many of these genes are direct LSD1 targets, we did not observe histone methylation changes at the LSD1-bound regions, demonstrating non-canonical histone demethylation-independent mechanisms of gene regulation. This ChIP-seq dataset included H3K4me2 and H3K9me2 ChIP-seq data for siRNA target against LSD1 and non-targeting control, as well as SP2509 inhibition of LSD1 and mock treatment 4 conditions: siRNA against LSD1, siRNA against luciferase (non-targeting control); SP2509 inhibition of LSD1, mock treatment. There are 2 replicates per condition.

2016-06-30 | E-GEOD-77762 | biostudies-arrayexpress

Dynamics of de novo heterochromatin assembly and disassembly at replication forks ensures fork stability

Project description:Chromatin is dynamically reorganized when DNA replication forks are challenged. However, the process of epigenetic reorganization and its implication for fork stability is poorly understood. Here, we discover a checkpoint regulated cascade of chromatin signaling that activates 5 the histone methyltransferase EHMT2/G9a to catalyze heterochromatin assembly at stressed replication forks. Using biochemical and single molecule chromatin fiber approaches, we show that G9a together with SUV39h1 induces chromatin compaction by accumulating the repressive modifications, H3K9me1/me2/me3, in the vicinity of stressed replication forks. This closed conformation is also favored by the G9a-dependent exclusion of the H3K9-demethylase 10 JMJD1A/KDM3A, which facilitates heterochromatin disassembly upon fork restart. Untimely heterochromatin disassembly from stressed forks by KDM3A enables PRIMPOL access, triggering ssDNA gap formation and sensitizing cells towards chemotherapeutic drugs. These findings may help explaining chemotherapy resistance and poor prognosis observed in cancer patients displaying elevated level of G9a/H3K9me3.

2023-05-12 | PXD041742 | Pride

Specific phosphorylation of histone demethylase KDM3A determines target gene expression in response to heat shock

Project description:Histone lysine (K) residues, which are modified by methyl- and acetyl-transferases, diversely regulate RNA synthesis. Unlike the ubiquitously activating effect of histone K acetylation, the effects of histone K methylation vary with the number of methyl groups added and with the position of these groups in the histone tails. Histone K demethylases (KDMs) counteract the activity of methyl-transferases and remove methyl group(s) from specific K residues in histones.KDM3A (also known as JHDM2A or JMJD1A) is an H3K9me2/1 demethylase. KDM3Aperforms diverse functions via the regulation of its associated genes, which are involved in spermatogenesis, metabolism, and cell differentiation. However, the mechanism by which the activity of KDM3A is regulated is largely unknown. First, we demonstrated that mitogen- and stress-activated protein kinase 1 (MSK1) specifically phosphorylates KDM3A at Ser264 (pKDM3A), which is enriched in the regulatory regions of gene loci in the human genome under heat shock conditions. p-KDM3A directly interacts with and is recruited by the transcription factor Stat1 to activate KDM3A target genes. The demethylation of H3K9me2 at the Stat1 binding site specifically depends on the co-expression of p-KDM3A under heat shock conditions. In contrast to heat shock treatment, IFN-M-NM-3 treatment does not phosphorylate KDM3A via MSK1, thereby abrogating its downstream effects. To our knowledge, this is the first evidence that a KDM can be modified via phosphorylation to determine its specific binding to target genes in response to cellular stress. 3 ChIP samples and two input as controls

2014-10-15 | E-GEOD-62309 | biostudies-arrayexpress

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