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: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:H3K27ac ChIP-Seq data of the B-ALL cell lines REH and 697 were obtained to find active regions in the genome and to correlate that with expression profiling of lncRNAs in these cell lines.
Project description:This dataset contains RNA-seq, ATAC-seq, and ChIP-seq samples from the SJERG cohort. We applied ChIP-Seq for Dux4 on two B-cell ALL cell-lines(REH, Nalm6) along with INPUT. ATAC-Seq on two B-cell ALL cell-lines(REH, Nalm6) and xenograft of a B-cell ALL patient(ERG000016).
Project description:The goal of this study was to determine IGF2BP3 RNA targets in human B-cell Acute Lymphocitic Leukemia cell models. Included are iCLIP-seq libraries for IGF2BP3 from RS4;11 and REH B-ALL cell samples and RNA-seq data sets from control and IGF2BP3 knockdown RS4;11 B-ALL cell lines
Project description:The acute lymphoblastic leukemia cells lines JM-1, REH, Nalm-27, and SUP-B15 were analyzed for baseline expression of extacellular matrix and adhesion molecules using a pathway focused cDNA microarray (SABiosciences). RNA isolated from the ALL cell lines JM-1, REH, Nalm-27, and SUP-B15 was analyzed using the Extracellular Matrix and Adhesion Molecules Oligo GEArray (SABIosciences).
Project description:[Gro-seq] Precursor B acute leukemia cells measured using global nuclear run-on sequencing [ChIP-Seq] The genome-wide occupancy of ser2 and ser5 phosphorylated RNA pol2 and H3K4me3 was measured in precursor B acute leukemia cells measured using chip-seq. [Gro-seq] Nascent RNA expression profiles were generated at cells in various basal culture conditions. [ChIP-Seq] Performed from REH and Nalm6 cells cultured under basal culture conditions. Mnase digestion was used for DNA fragmentation. Antibodies against Ser2 and Ser5 phosphorylated RNA polymerase and H3K4me3 compared to input. ****************************** This study includes reanalysis of Samples in Series GSE39878 (GSM980645, GSM980644), GSE60454 (GSM1480326), and GSE41009 (GSM1006728, GSM100672). The processed data files for the reanalyses are linked to GSE67540 as supplementary files (see the GSE67540_README.txt file for additional information).
Project description:We report that retention of intron 2 which affects expression of CD19 in CART-19 relapsed leukemia occurs in the context of full length CD19 transcript using Oxford Nanopore sequencing technology. By performing Direct RNA sequencing on Reh leukemia cell lines, we showed that intron 2 retention is functionally equivalent to nonsense mutations.