Project description:Epigenetic aberrations are a hallmark of cancer; however, we have limited information on chromatin aberrations present in cancer cells. Here we provide genome-wide maps for histone modification binding for 6 reference histone markers in 145 cancer cell lines belonging to 9 cancer types generating 680 chromatin maps. NMF clustering for H3K27ac-defined enhancers classified cancer cells into 5 distinct subtypes. These subtypes were either correlated with the developmental trajectory of original tissue or cell phenotype such as mesenchymal features. We identify a cluster consisting of different tumor types but with a unique enhancer profile and its dependency on key oncogenes. Detailed characterization of bivalent state switches between cancer cells and their normal counterparts identified epithelial-to-mesenchymal driver transcription factors to be activated via this mechanism in breast, GBM and melanomas. Finally, we identify cancer-specific lengthening of H3K4me3 domains on oncogenes and their shortening on specific tumor-suppressors, respectively. Overall, our study provides epigenome reference maps for widely-used cancer cell lines which will be useful for discovery of important principles about chromatin mediated cancer gene regulation.
Project description:We have used a genome-wide ChIP-sequencing approach to define and investigate the dynamics of the cis-regulatory landscape in three developmental stages of the murine hematopoietic system. To this end, we have compared the profiles of H3K4me3, H3K4me1, H3K27ac, H3K27me3 and H3K9me2 in HSCs, committed pro-B and splenic mature B cells. We find the enhancer repertoire to be dynamically reshaped during hematopoiesis progression, surprisingly only a small fraction of primed enhancers in HSCs or committed progenitors become activated in subsequent stages. In turn, the majority of active enhancers in terminally differentiated cells are not primed in earlier stages. We also found that The heterochromatin mark H3K9me2 covers large domains that remain largerly invariant across the three stages and are depleted in both active chromatin marks and the Polycomb related mark H3K27me3. Investigating enhancer dynamics in 3 different stages of B cell development
Project description:We have used a genome-wide ChIP-sequencing approach to define and investigate the dynamics of the cis-regulatory landscape in three developmental stages of the murine hematopoietic system. To this end, we have compared the profiles of H3K4me3, H3K4me1, H3K27ac, H3K27me3 and H3K9me2 in HSCs, committed pro-B and splenic mature B cells. We find the enhancer repertoire to be dynamically reshaped during hematopoiesis progression, surprisingly only a small fraction of primed enhancers in HSCs or committed progenitors become activated in subsequent stages. In turn, the majority of active enhancers in terminally differentiated cells are not primed in earlier stages. We also found that The heterochromatin mark H3K9me2 covers large domains that remain largerly invariant across the three stages and are depleted in both active chromatin marks and the Polycomb related mark H3K27me3.
Project description:We report the application of high resolution MNase ChIP for high-throughput profiling of H3K27Ac and RNAPII in uterine fibroid tumors. Analysis revealed H3K27Ac remodeling at distal enhancer regions, highlighting the enrichment of AP-1 complex DNA binding motifs. ChIP-sequencing of AP-1 subunits JUN and FOS revealed differential occupancy of AP-1 at enhancer sites. In addition, ChIP-seq of CDK8 submodule subunits CDK8 and MED12 demonstrate differential CDK8 submodule occupancy consistent with remodelled enhancer regions.
Project description:H3K27ac is an active enhancer mark, which is associated with higher activation of transcription. To determine the downstream transcriptional targets and pathways of H3K27ac in PTEN-deficient glioblastoma, ChIP-seq was performed in SF763 PTEN-KO and U87 cells.
Project description:<p>In this study we profile the epigenomic enhancer landscapes of CLL B cells (CD19+/CD5+) harvested from peripheral blood of patients from our Center. Included are results of ChIPseq profiling using chromatin immunoprecipitation of the enhancer histone mark H3K27ac (acetylated lysine 27 on histone H3), and open chromatin profiles using ATAC-seq (assay for transposase accessible chromatin). These profiles are used to define the global enhancer and super enhancer landscape of CLL B cells, and to derive active transcription factor networks associated with this disease. Also included are H3K27ac ChIP-seq and ATAC-seq datasets for non-CLL B cells obtained from the peripheral blood of normal adult donors.</p>
Project description:Histone mark for active enhancer H3K27ac was studied using various melanoma cell lines. SMC1A level on chromatin was studied after knockdown of NIPBL in 501mel
Project description:We applied ChIP-seq technology for mapping chromatin modification in Th17 cells. We find that acetylations on histone H3 lysine 27, an active enhancer mark, significantly overlap with open chromatin as defined by ATAC-seq. These results were used to define putative super enhancer loci in Th17 cells. Our study shows that super-enhancer mediated gene transcription is important for Th17 effector functions.
Project description:We report high-throughput profiling of acetylation of lysine 27 on histone H3 from whole zebrafish ventricles. The H3K27Ac mark has been shown to be present at active enhancer elements and including regions of active chromatin. We profile H3K27Ac in uninjured cardiomyocytes and those undergoing regeneration 14 days after genetic ablation. This study provides a framework for understanding chromatin transitions during adult models of regeneration.
