Genome-wide maps of KDM5A/JARID1A/RBP2 and its isoforms in differentiated U937 cells
Ontology highlight
ABSTRACT: We report the identification of genomic regions bound by RBP2 isoforms and define the functional categories that these regions represent. RBP2 modifies methylated lysine residues on histone tails. We found that RBP2 large isoform containing the recognition module for histone H3K4me3 and RBP2 small isoform lacking this module bind to to different regions in the human genome. Importantly, isoform-specific regions and overlapping regions belong to genes with different molecular functions. For example, chromatin binding and transcription factor binding functions can be ascribed to gene targets of RBP2 small isoform but not of RBP2 large isoform. By comparing gene sets generated for all isoforms and RBP2 large isoform, we can define if the small isoform is specifically recruited to genomic regions dispaying certain signatures, such as transcription start sites, CpG-rich regions, transcriptional activity and transcription factor binding.
Project description:We report the identification of genomic regions bound by RBP2 in MCF7 (ER+) cells and the MCF7 cells that were treated with estradiol. RBP2 is recruited to TSS regions and shows preference for GC-rich regions. We find the regions differentially bound by RBP2 after estrogen treatment. These regions will be correlated with binding of ER, H2A.Z and high/low transcriptional activity. We also report genomic regions bound by RBP2 closest homolog, PLU1. PLU1 location does not overlap with RBP2 binding sites. In contrast to RBP2, PLU1 does not show very high enrichment at TSS. This suggests that these two histone demethylases are preferentially located in different regions.
Project description:We sought to determine H3K4me3 distribution in mouse embryonic stem (ES) cells deficient for RBP2 compared with wild-type cells. RBP2 modifies methylated lysine residues on histone tails. As a result of this analysis, we identified genomic regions with changed H3K4me3 status and described these in gene ontology (GO) categories.
Project description:We report the identification of genomic regions bound by RBP2 and JARID2 in mouse cardiomyocytes. RBP2 generates methylated lysine 4 in histone H3. Consistent with previous data, RBP2 binds at the TSS regions. However, we found that overepresentation of gene ontologies (GO) for RBP2 targets in cardiomyocytes is drastically different from those in mouse embryonic stem (ES) cells. In cardiomyocytes, there is overepresentation of genes involved in heart morphogenesis and vasculogenesis. Strikingly, we found that location of JARID2, a factor critical for ES cell function, significantly overlaps with RBP2 location in cardiomyocytes.
Project description:We sought to determine H3K4me3 distribution in mouse embryonic stem (ES) cells deficient for RBP2 compared with wild-type cells. RBP2 modifies methylated lysine residues on histone tails. As a result of this analysis, we identified genomic regions with changed H3K4me3 status and described these in gene ontology (GO) categories. Examination of histone methylation in the absence of histone demethylase RBP2
Project description:RBP2 (JARID1A/RBBP2) enrichment at proximal promoter regions in differentiating promonocytic U937 cells and in the osteosarcoma SAOS-2 cells Keywords: differentiation treatment, ChIP-on-chip analysis
Project description:RBP2 (JARID1A/RBBP2) enrichment at proximal promoter regions in differentiating promonocytic U937 cells and in the osteosarcoma SAOS-2 cells Keywords: differentiation treatment, ChIP-on-chip analysis We sought to determine transcriptional regulation by RBP2 genome-wide by using location analysis. We describe that RBP2 target genes are separated into two functionally distinct classes: differentiation independent and differentiation dependent genes.Three condition experiment, U937 cells treated with 100 nM 12-O-tetradeconoyl-phorbol 13-acetate (TPA) (Sigma) for two different time points (27 hrs and 96 hrs) and untreated (0 hrs time point or no TPA treatment). In addition, processed data for the unrelated SAOS-2 cells are included. Biological replicates: threechromatin immunoprecipitations (ChIP) performed independently in parallel
Project description:Aberrations in epigenetic processes, such as histone methylation, can lead to cancer. Retinoblastoma Binding Protein 2 (RBP2)(also called JARID1A or KDM5A) can demethylate tri- and di-methylated lysine 4 in histone H3, which are epigenetic marks for transcriptionally active chromatin, whereas the MEN1 tumor suppressor promotes H3K4 methylation. Previous studies suggested that inhibition of RBP2 contributed to tumor suppression by pRB. Here we show RBP2 loss promotes cellular differentiation in vitro. We use mouse expression array 430 2.0 array to profile gene expression patterns of Rbp2f/f and Rbp2-/- ES cells in ES cell medium and after 6 days in ES cell medium without LIF.
Project description:To identify genes whose expression was affected by RBP2, we performed gene expression microarray analysis in control and RBP2 depletion human lung cancer cell line. Two individual shRNA (RBP2 KD1 and RBP2 KD2) were used to limit potential off-target effects.
Project description:RBP2 is downstream of pRB pathway We used gene expression profiling experiments to investigate if gene expression changes in cells with RBP2 knockdown significantly overlap with gene expression changes in cells overexpressing pRB, consistent with the data that knockdown of RBP2 phenocopies reintroduction of pRB in SAOS-2 (RB-/-) cells Keywords: epistatic experiment
Project description:The roles of histone demethylase RBP2 in gene expression were assessed using gene expression profiling experiments with wild type and RBP2-/- primary MEFs. Several cytokine genes including SDF1 and Kit ligand were upregulated upon inactivation of RBP2. Keywords: mouse embryonic fibroblasts, gene expression profiling, microarray, Affymetrix Mouse Genome 430 2.0, cell type comparison