DNMT3A epigenetically regulates key microRNAs involved in epithelial-to-mesenchymal transition in prostate cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB41664 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR4903892.fastq.gz | Fastqsanger.gz | |||
| ERR4903893.fastq.gz | Fastqsanger.gz | |||
| ERR4903894.fastq.gz | Fastqsanger.gz | |||
| ERR4903895.fastq.gz | Fastqsanger.gz | |||
| ERR4903896.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
Similar Datasets
Project description:Epithelial-to-Mesenchymal Transition (EMT) is involved in prostate cancer metastatic progression and its plasticity suggests epigenetic implications. Deregulation of UHRF1/DNMT1, DNMT3A and miRNAs play a role in EMT, but their interplay has not been clarified yet. Here, we identify miR-720 and miR-1260a as new DNMT3A regulators through miRNA microarray performed on UHRF1 silenced Androgen Receptor (AR) non-responsive (PC3) cell extracts, and subsequent target validation and functional overexpression and downregulation in PC3 and AR responsive LNCaP cells, respectively. These miRNAs inversely correlated with DNMT3A in our ex-vivo model of EMT in PC3 but not in LNCaP cells, induced with conditioned media from patient-derived Cancer-Associated Fibroblasts (CM-CAF). miR-720 and miR-1260a were expressed in very few patients from the PRAD TCGA data set expressing an EMT or MET (Mesenchymal-to-Epitelial Transition) signature; miR-200 family (miR-200a/b, -141, -429), along with miR-205 and miR-203, were downregulated in EMT patients as they modulate key EMT factors. These latter miRNAs resulted hyper-methylated at their promoters in our ex-vivo EMT prostate cancer model, while in the EMT PRAD TCGA data set only miR200c and miR141 promoters displayed a diffused hyper-methylated pattern inversely correlated with their transcriptional expression. Chromatin immunoprecipitation experiments performed on CM-CAF induced PC3 cells extracts showed that DNMT3A gets recruited onto the promoters of the latter two miRNAs, coupled with a marked increase of H3K27me3 and H3K9me3 and/or the decrease of H3K4me3 and H3K36me3. Altogether, our results point to a DNMT3A regulatory role of key miRNAs for EMT in prostate cancer.
2021-11-20 | E-MTAB-9835 | biostudies-arrayexpress
Project description:Hematopoietic stem cells (HSCs) are defined by their capacity to regenerate all main components of the peripheral blood, but individual HSCs exhibit a range of preferences for generating downstream cell types. Their propensities are thought to be epigenetically encoded, but no differential regulatory mechanisms have been identified. Here, we considered whether DNA methyltransferase 3A (DNMT3A) has a role in determining the differentiation choice of HSCs. We find that the most primitive megakaryocyte-biased HSCs depend most on DNMT3A for efficient hematopoietic regeneration, particularly of the lymphoid lineages. Reduced DNMT3A amplifies the biased HSC behavior. DNMT3A also regulates megakaryocyte and platelet output in part through DNA methylation at key megakaryocyte lineage loci. Together, our findings establish the role of epigenetic regulation in the fate of megakaryocyte-biased HSCs and their downstream progeny and suggest that the outcomes of DNMT3A-mutant clonal hematopoiesis and malignancies might vary depending on the identity of the HSC that acquires the mutation.
2025-02-17 | GSE276903 | GEO
Project description:Hematopoietic stem cells (HSCs) are defined by their capacity to regenerate all main components of the peripheral blood, but individual HSCs exhibit a range of preferences for generating downstream cell types. Their propensities are thought to be epigenetically encoded, but no differential regulatory mechanisms have been identified. Here, we considered whether DNA methyltransferase 3A (DNMT3A) has a role in determining the differentiation choice of HSCs. We find that the most primitive megakaryocyte-biased HSCs depend most on DNMT3A for efficient hematopoietic regeneration, particularly of the lymphoid lineages. Reduced DNMT3A amplifies the biased HSC behavior. DNMT3A also regulates megakaryocyte and platelet output in part through DNA methylation at key megakaryocyte lineage loci. Together, our findings establish the role of epigenetic regulation in the fate of megakaryocyte-biased HSCs and their downstream progeny and suggest that the outcomes of DNMT3A-mutant clonal hematopoiesis and malignancies might vary depending on the identity of the HSC that acquires the mutation.
2025-02-17 | GSE276901 | GEO
Project description:Hematopoietic stem cells (HSCs) are defined by their capacity to regenerate all main components of the peripheral blood, but individual HSCs exhibit a range of preferences for generating downstream cell types. Their propensities are thought to be epigenetically encoded, but no differential regulatory mechanisms have been identified. Here, we considered whether DNA methyltransferase 3A (DNMT3A) has a role in determining the differentiation choice of HSCs. We find that the most primitive megakaryocyte-biased HSCs depend most on DNMT3A for efficient hematopoietic regeneration, particularly of the lymphoid lineages. Reduced DNMT3A amplifies the biased HSC behavior. DNMT3A also regulates megakaryocyte and platelet output in part through DNA methylation at key megakaryocyte lineage loci. Together, our findings establish the role of epigenetic regulation in the fate of megakaryocyte-biased HSCs and their downstream progeny and suggest that the outcomes of DNMT3A-mutant clonal hematopoiesis and malignancies might vary depending on the identity of the HSC that acquires the mutation.
2025-02-17 | GSE287996 | GEO
Project description:Hematopoietic stem cells (HSCs) are defined by their capacity to regenerate all main components of the peripheral blood, but individual HSCs exhibit a range of preferences for generating downstream cell types. Their propensities are thought to be epigenetically encoded, but no differential regulatory mechanisms have been identified. Here, we considered whether DNA methyltransferase 3A (DNMT3A) has a role in determining the differentiation choice of HSCs. We find that the most primitive megakaryocyte-biased HSCs depend most on DNMT3A for efficient hematopoietic regeneration, particularly of the lymphoid lineages. Reduced DNMT3A amplifies the biased HSC behavior. DNMT3A also regulates megakaryocyte and platelet output in part through DNA methylation at key megakaryocyte lineage loci. Together, our findings establish the role of epigenetic regulation in the fate of megakaryocyte-biased HSCs and their downstream progeny and suggest that the outcomes of DNMT3A-mutant clonal hematopoiesis and malignancies might vary depending on the identity of the HSC that acquires the mutation.
2025-02-17 | GSE287995 | GEO
Project description:DNA methyltransferase 3A (DNMT3A) plays a critical role in establishing and maintaining DNA methylation patterns, essential for the dynamic organization of vertebrate genomes. However, the mechanisms underlying DNMT3A1's recruitment and function within different chromatin environments remain unclear. We find that DNMT3A interacts with modified nucleosomes through multivalent interactions, involving both direct binding to chromatin features and site-specific post-translational histone modifications.
2024-12-07 | PXD046529 | Pride
Project description:Transcriptional profiling of mouse lung tumors comparing Dnmt3a KO/K-ras G12D mutant with Dnmt3a WT/K-ras G12D mutant. The goal is to search for the difference of mRNA abundance between Dnmt3a KO and WT tumors. Two-condition experiment, KO vs. WT tissure. Biological replicates: 12.
2011-10-25 | E-GEOD-32415 | biostudies-arrayexpress
Project description:DNA methyltransferase 3A (DNMT3A) plays a critical role in establishing and maintaining DNA methylation patterns. However, the mechanisms underlying DNMT3A recruitment to and function within different chromatin environments remain unclear. Using a combination of biochemical and structural approaches we find that DNMT3A interacts using multiple interfaces with chromatin; directly binding generic nucleosome features as well as site-specific post-translational histone modifications. The N-terminal region, unique to the DNMT3A1 isoform, is essential for these interactions and stabilises H3K36me2-nucleosome recruitment. Intriguingly, in the same region critical for nucleosome binding we also map a ubiquitylation-dependent recruitment motif (UDR). The UDR binds specifically to ubiquitylated H2AK119, explaining the previously observed recruitment to Polycomb-occupied heterochromatin. A cryo-EM structure of DNMT3A1-DNMT3L with a modified nucleosome reveals that the UDR interacts with the nucleosome surface including the acidic patch. Previously unexplained disease-associated mutations are present in the UDR and ablate nucleosome interactions. This leads to an increased understanding of how DNMT3A1 recruitment occurs in the genome and highlights the importance of multivalent binding of DNMT3A to histone modifications and the nucleosome.
2024-10-16 | PXD056554 | Pride
Project description:Transcriptional profiling of mouse lung tumors comparing Dnmt3a KO/K-ras G12D mutant with Dnmt3a WT/K-ras G12D mutant. The goal is to search for the difference of mRNA abundance between Dnmt3a KO and WT tumors.
2011-10-26 | GSE32415 | GEO
Project description:To examine whether Dnmt3a deficiency resulted in genomic methylation changes we performed an unbiased methylome analysis. Methylated DNA isolated from three Dnmt3a deficient and two WT tumors was immunoprecipitated and subjected to high throughput sequencing (MeDIP-Seq). We observed that genes that were less expressed in Dnmt3a deficient tumors tended to have lower methylation levels in gene bodies. Examination of methylcytosine in two tumor types
2011-10-25 | E-GEOD-32484 | biostudies-arrayexpress