Synthetic construct
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA318031 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3356371.fastq.gz | Fastqsanger.gz | |||
| SRR3356372.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 2 of 2 |
Similar Datasets
Project description:Ewing Sarcoma is the second most common solid pediatric malignant neoplasm of the bone and soft tissue. Driven by EWS/Ets, or rarely variant, oncogenic fusions, Ewing Sarcoma is a biologically and clinically aggressive disease with a high propensity for metastasis. Our laboratory has previously identified the Jumonji-domain H3K9 me 1/2 histone demethylase KDM3A as a novel oncogene downstream of EWS/Fli1, the most common oncofusion in Ewing Sarcoma. Herein, we uncover a role for KDM3A in the promotion of Ewing Sarcoma metastasis. Using global gene expression profiling, we show that some of the most strongly regulated genes by KDM3A are those implicated in cell migration and metastasis, and demonstrate, using functional assays, that KDM3A promotes migration in vitro and metastasis in vivo. We further provide evidence that MCAM, one of the most strongly and consistently regulated genes by KDM3A, is an important effector of KDM3A pro-metastatic action. Our studies also show that KDM3A regulates MCAM expression both through a direct mechanism, involving modulation of H3K9 methylation at the MCAM promoter, and an indirect mechanism, via the Ets1 transcription factor.
2017-02-08 | GSE94619 | GEO
Project description: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.
2019-05-15 | GSE109748 | GEO
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
Project description:Histone modifying enzymes play a central role in maintaining cell identity by establishing a conducive chromatin environment for lineage specific transcription factor activity. Pluripotent embryonic stem cells (ESCs) identity is characterized by lower abundance of gene repression associated histone modifications that enables rapid response to differentiation cues. The KDM3 histone demethylase family removes the repressive histone H3 lysine 9 dimethylation (H3K9me2). Here we uncover a surprising role for the KDM3 proteins in the maintenance of the pluripotent state through post-transcriptional regulation. We find through immunoaffinity purification of the KDM3A or KDM3B interactome and proximity ligation assays that KDM3A and KDM3B interact with RNA processing factors such as EFTUD2 and PRMT5. By generating double “degron” ESCs to degrade KDM3A and KDM3B in the rapid timescale of splicing, we find altered splicing, independent of H3K9me2 status. These splicing changes partially resemble the splicing pattern of the more blastocyst-like ground state of pluripotency and occurred in important chromatin and transcription factors such as Dnmt3b, Tbx3 and Tcf12. Our findings reveal non-canonical roles of histone modifying enzymes in splicing to regulate cell identity.
2025-06-23 | PXD042735 | Pride
Project description:Histone modifications, including N-lysine acetylation and methylation, play critical roles in eukaryotic transcription. The addition of acetyl- and methyl-groups and removal of acetyl-groups involves redox neutral reactions, whereas demethylation is O2 dependent, a reaction with potential to enable O2 availability mediated regulation, as occurs for reactions catalysed by the 2-oxoglutarate dependent hypoxia-inducible factor (HIF) hydroxylases. A screen for substrates of the HIF-regulated Jumonji-C (JmjC) lysine demethylase KDM3A led to the finding that purified recombinant KDM3A catalyses oxidation of the N-acetyl group of Lys-9 of histone H3 giving an N-hydroxyacetyl-lysine residue. Studies employing a N-hydroxyacetyl-lysine selective antibody and mass spectrometry support the cellular relevance of N-hydroxyacetyl-lysine. The combined biochemical and cellular results reveal evidence for an unanticipated O2-mediated link between histone lysine N-acetylation and JmjC catalysis. Future work can explore the biological significance of N-hydroxyacetylation, including in the hypoxic response where KDM3A plays a role in regulating HIF target genes.
2026-02-09 | PXD057969 | Pride
Project description:To understand transcriptome and epigenome profilings alteration during breast cancer initiation and development, we constructed a in vitro breast cancer transformation model. And then, we use mRNA-Seq to uncover differential expression genes during breast cancer transformation process. For epigenomic profilings, we specificly analysis genome wide H3K9me2, H3K9me3,H3K4me3 and H3K27me3 modifications using ChIP-Seq. We found that H3K9 di and tri methylation decrease both in vitro breast cancer cell transformation model and in vivo clinical samples. Further more, we found KDM3A, a demethylase for H3K9 mono and di methylation, increase during the breast cancer model transformation process and clinical samples. KDM3A deficiency impairs the growth of those transformed cell lines and its overexpression promotes tumor formation.
2016-04-08 | GSE64367 | GEO
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
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
Project description:Heart disease and failure is a leading cause of mortality worldwide. Left ventricular hypertrophy (LVH) is a major risk factor for cardiovascular morbidity and mortality and the development of heart failure. Pathological LVH induced by sustained pressure-overload engages transcriptional programs including reactivation of canonical fetal genes and those inducing fibrosis. Histone lysine demethylases (KDMs) are emerging potent regulators of transcriptional reprogramming in cancer, though their potential role in abnormal growth and fibrosis in heart disease remains little understood. Here, we investigated gain and loss of function of an H3K9me2 specific demethylase, Kdm3a, in myocytes and in vivo, and show it promotes LVH and myocardial fibrosis in response to pressure-overload. Cardiomyocyte KDM3A activates the transcription of tissue-inhibitor of MMP type 1 (Timp1) with pro-fibrotic activity. By contrast, a pan-KDM inhibitor, JIB-04, suppresses TAC-induced LVH and fibrosis. JIB-04 inhibits KDM3A and suppresses the transcription of fibrotic genes that overlap with genes downregulated in Kdm3a-KO mice versus WT controls. Our study provides genetic and biochemical evidence for a pro-hypertrophic function of KDM3A and proof-of principle for pharmacological targeting of KDMs as an effective strategy to counter LVH and pathological fibrosis.
2018-10-09 | GSE120739 | GEO
Project description:KDM3A catalysed formation of hydroxyacetyl-lysine on histone H3K9
| PRJNA1188125 | ENA