Similar Datasets
Project description:Protein arginine methyltransferase 6 (PRMT6) is an epigenetic regulator of fundamental cellular processes, such as gene expression and DNA repair. Asymmetric dimethylation of histone H3 at arginine 2 (H3R2me2a) is the major histone modification catalyzed by PRMT6. To identify the genome-wide deposition and transcriptional impact of H3R2me2a, we established PRMT6 deletion in a human cell model of neural differentiation. These knockout cells show severe neural differentiation defects. ChIP-seq profiling reveals that H3R2me2a is present at promoter as well as non-promoter sites in a PRMT6-dependent manner. Loss of H3R2me2a causes enhanced H3K4me3 deposition and target gene transcription supporting a genome-wide repressive nature of H3R2me2a. Intriguingly, the non-promoter H3R2me2a peaks co-localize with active enhancer marks, such as H3K4me1 and H3K27ac.
2018-09-27 | GSE117200 | GEO
Project description:Genomic location of PRMT6-dependent H3R2 methylation is decisive for the transcriptional outcome of associated genes
| PRJNA420761 | ENA
Project description:Genomic location of PRMT6-dependent H3R2 methylation is decisive for the transcriptional outcome of associated genes [ChIP-seq]
| PRJNA481455 | ENA
Project description:Protein arginine methyltransferase 6 (PRMT6) is an epigenetic regulator of fundamental cellular processes, such as gene expression and DNA repair. Asymmetric dimethylation of histone H3 at arginine 2 (H3R2me2a) is the major histone modification catalyzed by PRMT6. To identify the genome-wide deposition and transcriptional impact of H3R2me2a, we established PRMT6 deletion in a human cell model of neural differentiation. These knockout cells show severe neural differentiation defects. ChIP-seq profiling reveals that H3R2me2a is present at promoter as well as non-promoter sites in a PRMT6-dependent manner. Loss of H3R2me2a causes enhanced H3K4me3 deposition and target gene transcription supporting a genome-wide repressive nature of H3R2me2a. Intriguingly, the non-promoter H3R2me2a peaks co-localize with active enhancer marks, such as H3K4me1 and H3K27ac.
2018-09-27 | GSE107609 | GEO
Project description:Protein arginine methyltransferase 6 (PRMT6) is known to catalyze the generation of asymmetric dimethylarginine in polypeptides. Although the cellular role of PRMT6 is not well understood, it has been implicated in human immunodeficiency virus pathogenesis, DNA repair, and transcriptional regulation. PRMT6 is known to methylate histone H3 Arg-2 (H3R2), and this negatively regulates the lysine methylation of H3K4 resulting in gene repression. To identify in a nonbiased manner genes regulated by PRMT6 expression, we performed a microarray analysis on U2OS osteosarcoma cells transfected with control and PRMT6 small interfering RNAs. We identified thrombospondin-1 (TSP-1), a potent natural inhibitor of angiogenesis, as a transcriptional repression target of PRMT6. Moreover, we show that PRMT6-deficient U2OS cells exhibited cell migration defects that were rescued by blocking the secreted TSP-1 with a neutralizing peptide or blocking alpha-TSP-1 antibody. PRMT6 associates with the TSP-1 promoter and regulates the balance of methylation of H3R2 and H3K4, such that in PRMT6-deficient cells H3R2 was hypomethylated and H3K4 was trimethylated at the TSP-1 promoter. Using a TSP-1 promoter reporter gene, we further show that PRMT6 directly regulates the TSP-1 promoter activity. These findings show that TSP-1 is a transcriptional repression target of PRMT6 and suggest that neutralizing the activity of PRMT6 could inhibit tumor progression and therefore may be of cancer therapeutic significance.
| S-EPMC2755858 | biostudies-other
Project description:The huntingtin (HTT) protein transports various organelles, including vesicles containing neurotrophic factors, from embryonic development throughout life. To better understand how HTT mediates axonal transport and why this function is disrupted in Huntington's disease (HD), we study vesicle-associated HTT and find that it is dimethylated at a highly conserved arginine residue (R118) by the protein arginine methyltransferase 6 (PRMT6). Without R118 methylation, HTT associates less with vesicles, anterograde trafficking is diminished, and neuronal death ensues-very similar to what occurs in HD. Inhibiting PRMT6 in HD cells and neurons exacerbates mutant HTT (mHTT) toxicity and impairs axonal trafficking, whereas overexpressing PRMT6 restores axonal transport and neuronal viability, except in the presence of a methylation-defective variant of mHTT. In HD flies, overexpressing PRMT6 rescues axonal defects and eclosion. Arginine methylation thus regulates HTT-mediated vesicular transport along the axon, and increasing HTT methylation could be of therapeutic interest for HD.
| S-EPMC8132453 | biostudies-literature
Project description:BackgroundCovalent histone modifications are central to all DNA-dependent processes. Modifications of histones H3 and H4 are becoming well characterised, but knowledge of how H2A modifications regulate chromatin dynamics and gene expression is still very limited.ResultsTo understand the function of H2A modifications, we performed a systematic analysis of the histone H2A methylation status. We identified and functionally characterised two new methylation sites in H2A: R11 (H2AR11) and R29 (H2AR29). Using an unbiased biochemical approach in combination with candidate assays we showed that protein arginine methyltransferase (PRMT) 1 and PRMT6 are unique in their ability to catalyse these modifications. Importantly we found that H2AR29me2 is specifically enriched at genes repressed by PRMT6, implicating H2AR29me2 in transcriptional repression.ConclusionsOur data establishes R11 and R29 as new arginine methylation sites in H2A. We identified the specific modifying enzymes involved, and uncovered a novel functional role of H2AR29me2 in gene silencing in vivo. Thus this work reveals novel insights into the function of H2A methylation and in the mechanisms of PRMT6-mediated transcriptional repression.
| S-EPMC3164600 | biostudies-literature
Project description:DNA methylation is an important epigenetic modification that has been repeatedly implied in organismal adaptation. However, many previous studies that have linked DNA methylation patterns to environmental parameters have been limited by confounding factors, such as cell-type heterogeneity and genetic variation. In this study, we analyzed DNA methylation variation in marbled crayfish, a clonal and invasive freshwater crayfish that is characterized by a largely tissue-invariant methylome and negligible genetic variation. Using a capture-based subgenome bisulfite sequencing approach that covers a small, variably methylated portion of the marbled crayfish genome, we identified specific and highly localized DNA methylation signatures for specimens from geographically and ecologically distinct wild populations. These results were replicated both biologically and technically by re-sampling at different time points and by using independent methodology. Finally, we show specific methylation signatures for laboratory animals and for laboratory animals that were reared at a lower temperature. Our results thus demonstrate the existence of context-dependent DNA methylation signatures in a clonal animal.
| S-EPMC8695926 | biostudies-literature
Project description:Genomic occurrence analysis of PRMT6-dependent H3R2me2a
| PRJNA420759 | ENA
Project description:Background/aimsMethylation status plays a causal role in carcinogenesis in targeted tissues. However, the relationship between the DNA methylation status of multiple genes in blood leukocytes and colorectal cancer (CRC) susceptibility as well as interactions between dietary factors and CRC risks are unclear.MethodsWe performed a case-control study with 466 CRC patients and 507 cancer-free controls to investigate the association among the methylation status of individual genes, multiple CpG site methylation (MCSM), multiple CpG site heterogeneous methylation and CRC susceptibility. Peripheral blood DNA methylation levels were detected by performing methylation-sensitive high-resolution melting.ResultsTotal heterogeneous methylation of CA10 and WT1 conferred a significantly higher risk of CRC (adjusted odds ratio [ORadjusted], 5.445; 95% confidence interval [CI], 3.075 to 9.643; ORadjusted, 1.831; 95% CI, 1.100 to 3.047; respectively). Subjects with high-level MCSM (MCSM-H) status demonstrated a higher risk of CRC (ORadjusted, 4.318; 95% CI, 1.529 to 12.197). Additionally, interactions between the high-level intake of fruit and CRH, WT1, and MCSM on CRC were statistically significant.ConclusionsThe gene methylation status of blood leukocytes may be associated with CRC risk. MCSM-H of blood leukocytes was associated with CRC, especially in younger people. Some dietary factors may affect hypermethylation status and influence susceptibility to CRC.
| S-EPMC5832342 | biostudies-literature