Similar Datasets
Project description:Proper functioning of the lymphatic system is required for normal immune response, fluid balance and lipid reabsorption. Multiple regulatory mechanisms are employed to ensure correct formation of lymphatic vessels; however, whether epigenetic regulation is involved in this process remains largely unknown. We report that epigenetic priming by the Disruptor of telomeric silencing 1-like (DOT1L) in endothelial cell (EC) is indispensable for generation and function of lymphatic endothelial cells (LECs). Loss function of DOT1L leads to reduction of H3K79 di-methylation and expression of the genes important for LEC development and function. Thus, our study establishes DOT1L-mediated transcriptional regulation in ECs plays an important role in differentiation and function of LECs.
2018-10-10 | GSE104809 | GEO
Project description:Proper functioning of the lymphatic system is required for normal immune response, fluid balance and lipid reabsorption. Multiple regulatory mechanisms are employed to ensure correct formation of lymphatic vessels; however, whether epigenetic regulation is involved in this process remains largely unknown. We report that epigenetic priming by the Disruptor of telomeric silencing 1-like (DOT1L) in endothelial cell (EC) is indispensable for generation and function of lymphatic endothelial cells (LECs). Mechanistically, loss function of DOT1L leads to reduction of H3K79 di-methylation and expression of the genes important for LEC development and function. Thus, our study establishes DOT1L-mediated transcriptional regulation in ECs plays an important role in differentiation and function of LECs.
2018-10-10 | GSE104810 | GEO
Project description:DOT1L as methyltransferase of H3K79 is implicated in brian development. Here, we further defined DOT1L function within the granular neurons during cerebellar development using ChIP-seq of H3K79 dimethylation of isolated cerebellar granular neurons and progenitors. Thereby we compared samples treated with a DOT1L inhibitor versus DMSO treated cells. The data sets reveals new important targets of DOT1L, which ensure a correct development of the cerebellum.
2018-10-15 | GSE101947 | GEO
Project description:We report the application of ChIP sequencing technology for high-throughput profiling of H3K79me2 in prostate cancer cells. We generated genome-wide maps of LNCaP and PC3 cells that were treated with the specific DOT1L inhibitor EPZ004777. We find that lysine 79 dimethylation is sensitive to DOT1L inhibition in both cell lines, however the enrichment of K79 methylated peaks differed between the two cell lines.
2019-08-09 | GSE135574 | GEO
Project description:Chromosome 3p monosomy is associated with a poor clinical outcome of patients with uveal melanoma. Since a copy of the tumor suppressor miR-16 gene is lost for these patients, we postulated that a 3p loss may reduce the miR-16 amount and activity, promoting RNA derepression and tumor burden (loss of brake effect) as observed in chronic lymphocytic leukemia. Unexpectedly, we found that miR-16 expression level is not decreased despite the 3p monosomy. In contrast, our results suggested that miR-16 activity is impaired in uveal melanoma. Here, we investigated the molecular mechanism explaining the sequestration of miR-16 by RNAs. By defining the miR-16 interactome, two genes sets have been highlighted, suggesting two divergent miR-16 functions. In addition to the canonical miR-16 targets such as CCND3 and CDC25A, we identified another set of miR-16-interacting RNAs called thereafter miR-16 sponges. miR-16 binds to these RNAs sponge without inducing their decay. Mechanistically, the miR-16/RNA non-canonical base-pairing promoted stability of mRNAs involved in cancer cell proliferation. The biological relevance has been challenged in uveal melanoma. We showed that patients with poor overall survival expressed higher levels of miR-16 sponges and canonical miR-16 targets. These results strongly suggested that miR-16 is no longer able to repress its targets and, in contrast, promotes RNA stability and protein expression of oncogenes. miR-16 activity assessment using our Sponge-signature discriminates the patient’s overall survival as efficiently as the current method based on copy number variations and driver mutations detection. To conclude, miRNA loss of function due to miRNA sequestration seems to promote cancer burden by two combined events – 'loss of brake and an acceleration'. Our results highlight the oncogenic role of the non-canonical base-pairing between miRNAs/mRNAs in uveal melanoma.
2022-10-04 | E-MTAB-10940 | biostudies-arrayexpress
Project description:In this study, we identified a multi-kinase inhibitor MTX-216 to be efficacious in blocking NF1 loss-of-function melanoma cells. To identify the mechansisms of action of MTX-216, we treated NF1 loss-of-function melanoma cell lines with MTX-216, MTX-211 (the structural analogue of MTX-216 that has no effect on melanoma cells) as well as commericial kinase inhibitors, trametinib and pictilisib, and compared their gene expression profiles.
2022-09-20 | GSE213588 | GEO
Project description:We transduced two individual murine KMT2A-MLLT3 AML samples with DOT1L and three days after sorting for DOT1L+ cells were collected for ChIP-Seq. Before beginning the ChIP protocol drosophila melanogaster (S2) cells were spiked in at a 1:2 ratio.
2019-07-10 | GSE134030 | GEO
Project description:Malignant melanoma is an aggressive, heterogeneous disease where new biomarkers for diagnosis and clinical outcome are needed. We searched for chromosomal aberrations that characterize its pathogenesis using 47 different melanoma cell lines and tiling-resolution BAC-arrays for comparative genomic hybridization. Major melanoma genes, including BRAF, NRAS, CDKN2A, TP53, CTNNB1, CDK4 and PTEN were examined for mutations. Distinct copy number alterations were detected, including loss or gain of whole chromosomes but also minute amplifications and homozygous deletions. Most common overlapping regions with losses were mapped to 9p24.3-q13, 10 and 11q14.1-qter whereas copy number gains were most frequent on chromosomes 1q, 7, 17q and 20q. Amplifications were delineated to oncogenes such as MITF (3p14), CCND1 (11q13), MDM2 (12q15), CCNE1 (19q12) and NOTCH2 (1p12). Frequent findings of homozygous deletions on 9p21 and 10q23 confirmed the importance of CDKN2A and PTEN. Pair-wise comparisons revealed distinct sets of alterations, e.g. mutually exclusive mutations in BRAF and NRAS, mutual mutations in BRAF and PTEN, concomitant chromosome 7 gain and 10 loss and concomitant chromosome 15q22.2-q26.3 gain and 20 gain. Moreover, alterations of the various melanoma genes were associated with distinct chromosomal imbalances suggestive of specific genomic programs in melanoma development. Keywords: comparative genomic hybridization
2007-03-06 | GSE6779 | GEO
Project description:Epigenetic regulators have emerged as critical factors governing the biology of cancer. Here, in the context of melanoma, we show that RNF2 is prognostic, exhibiting progression-correlated expression in human melanocytic neoplasms. Through a series of gain of function and loss of function studies, we establish that RNF2 is oncogenic and pro-metastatic. Mechanistically, RNF2-mediated invasive behavior is dependent on its ability to mono-ubiquitinate H2AK119 at the promoter of LTBP2, resulting in silencing of this negative regulator of TGFβ signaling. In contrast, RNF2's oncogenic activity did not require its catalytic activity nor derives from its canonical gene repression function, rather RNF2 drives proliferation through direct transcriptional up-regulation of the cell cycle regulator CCND2. In summary, RNF2 regulates distinct biological processes in the genesis and progression of melanoma via distinct molecular mechanisms, underscoring the complex and multi-faceted actions of epigenetic regulators in cancer. RNF2 is overexpressed in immortalized human melanocytes HMEL-BRAFV600E to address impact of RNF2 overexpression in melanoma and identify RNF2 target genes. ChIP was performed to identify RNF2 binding sites using antibody against the V5 tag.
2016-07-03 | E-GEOD-51929 | biostudies-arrayexpress
Project description:Although mutations in p53 are infrequent in human melanoma, its function is abnormal. In this study, whole genome bead arrays were used to examine the expression of p53 target genes in extracts from 6 melanoma cell lines, compared to extracts derived from diploid human melanocytes and fibroblasts, to provide a global assessment of aberrant p53 function. The expression of these genes was also examined in extracts derived from melanocytes and melanoma cell lines in which p53 expression had been inhibited using shRNA and compared to cells that had been transduced with a control shRNA. Total RNA extracted from 18 samples was analysed representing duplicates of 6 melanoma cell lines, 1 melanocyte cell line and 2 fibroblast cell lines. Melanoma cell lines were compared to normal cell lines. In addition, IgR3, Mel-RM and melanocyte cell lines were transduced with either control shRNA or p53 shRNA to evaluate the effect of p53 on its target genes. Cell lines transduced with control shRNA were compared to cell lines transduced with p53shRNA. Duplicates were analysed.
2011-12-01 | E-GEOD-29361 | biostudies-arrayexpress