Project description:Genome-wide DNA methylation profiling of human B-ALL cell line SEM after 48 h incubation with DMSO (control), CX-4945 (Silmitasertib), Decitabine (DEC) or combined CX-4945 + DEC treatment. The Infinium MethylationEPIC BeadChip was used to obtain DNA methylation profiles across approximately 866,895 CpG islands.
Project description:MLL-fusion proteins are potent inducers of cancer in hematopoietic cells, where they are known to cause changes in global gene expression. How MLL-fusion proteins interact with the genome has not been established, so we have limited understanding of the pathway by which these proteins generate aberrant gene expression programs. Here we describe how the MLL-AF4 protein occupies the genome in human leukemia cells and its striking effects on chromatin states. We find that the MLL-AF4 fusion protein selectively occupies regions of the genome that contain developmental regulatory genes important for hematopoietic stem cell identity and self-renewal. These MLL-AF4 bound regions have grossly altered chromatin structure, with histone modifications catalyzed by Trithorax Group (TrxG) proteins and Dot1 extending across unusually large domains. This indicates that a key feature of MLL-associated leukemogenesis is aberrant targeting of chromatin modifiers to regions of the genome controlling hematopoietic development. Our results define the direct targets of the MLL-fusion protein, reveal the global role of epigenetic misregulation in leukemia, and identify new targets for therapeutic intervention in human cancer. Keywords: cell type comparison This dataset includes expression data for two replicates each of SEM and REH leukemia cell lines and ChIP-chip data targeting RNAP2, H3K4me3, H3K79me2, ENL, AF4-C, and MLL-N in SEM and REH leukemia cell lines.
Project description:MLL-fusion proteins are potent inducers of cancer in hematopoietic cells, where they are known to cause changes in global gene expression. How MLL-fusion proteins interact with the genome has not been established, so we have limited understanding of the pathway by which these proteins generate aberrant gene expression programs. Here we describe how the MLL-AF4 protein occupies the genome in human leukemia cells and its striking effects on chromatin states. We find that the MLL-AF4 fusion protein selectively occupies regions of the genome that contain developmental regulatory genes important for hematopoietic stem cell identity and self-renewal. These MLL-AF4 bound regions have grossly altered chromatin structure, with histone modifications catalyzed by Trithorax Group (TrxG) proteins and Dot1 extending across unusually large domains. This indicates that a key feature of MLL-associated leukemogenesis is aberrant targeting of chromatin modifiers to regions of the genome controlling hematopoietic development. Our results define the direct targets of the MLL-fusion protein, reveal the global role of epigenetic misregulation in leukemia, and identify new targets for therapeutic intervention in human cancer. This dataset includes expression data for two replicates each of SEM and REH leukemia cell lines, ChIP-chip data targeting RNAP2, H3K4me3, H3K79me2, ENL, AF4-C, and MLL-N in SEM and REH leukemia cell lines, and ChIP-Seq data of H3K79me2, H3K4me3, ans WCE in SEM and REH cell lines. This Series contains the ChIP-Seq data only. The expression and ChIP-chip data are provided in GEO Series GSE13313.
Project description:Melanoma cell lines were established and used for methylome profiling with Illumina HM450 beadchip. The molecular alterations in selected invasive melanoma cell populations were compared to those in the original cell lines by performing DNA methylation (Illumina HM450K) assays
Project description:Effects of the pan-anti-apoptotic BCL-2 family small molecule inhibitor, obatoclax mesylate (GeminX Pharmaceuticals), on gene expression were evaluated by microarray analysis in order to gain insights into the killing mechanism by this compound in two human MLL-AF4 cell lines. The results of the gene expression profiling substantiated other lines of evidence derived from genetic and chemical cell death pathway inhibition, Western blot analysis, flow cytometric apoptosis assays, and electron microscopic analyses, showing triple apoptosis, autophagy, and necroptosis death pathway activation by this agent. The results also demonstrated modulation of a number of novel targets of obatoclax encoding various cell death factors at the gene expression level. SEM-K2 and RS4:11 cells were treated with obatoclax or vehicle for 6 hours. After treatment, total RNA was extracted and cRNA was prepared and hybridized with Affymetrix U133 Plus 2 microarrays. There were a total of 3 treatments per cell line (vehicle, obatoclax at the 72 h EC50, and obatoclax 3x 72 h EC50) and 2 biologic replicates per condition.