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H3K27M mutations resulting in epigenetic dysfunction are frequently observed in diffuse intrinsic pontine glioma (DIPGs), an incurable pediatric cancer. We conduct a CRISPR screen revealing that knockout of KDM1A encoding lysine-specific demethylase 1 (LSD1) sensitizes DIPG cells to histone deacetylase (HDAC) inhibitors. Consistently, Corin, a bifunctional inhibitor of HDACs and LSD1, potently inhibits DIPG growth in vitro and in xenografts. Mechanistically, Corin increases H3K27me3 levels suppressed by H3K27M histones, and simultaneously increases HDAC-targeted H3K27ac and LSD1-targeted H3K4me1 at differentiation-associated genes. Corin treatment induces cell death, cell-cycle arrest, and a cellular differentiation phenotype and drives transcriptional changes correlating with increased survival time in DIPG patients. These data suggest a strategy for treating DIPG by simultaneously inhibiting LSD1 and HDACs.
Pubmed ID: 31631026 RIS Download
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Computable knowledge regarding functions of genes and gene products. GO resources include biomedical ontologies that cover molecular domains of all life forms as well as extensive compilations of gene product annotations to these ontologies that provide largely species-neutral, comprehensive statements about what gene products do. Used to standardize representation of gene and gene product attributes across species and databases.
View all literature mentionsCharity registered in United Kingdom whose mission is to accelerate research in new areas of human biology and drug discovery.Not for profit, public-private partnership that carries out basic science of relevance to drug discovery whose core mandate is to determine 3D structures on large scale and cost effectively targeting human proteins of biomedical importance and proteins from human parasites that represent potential drug targets.
View all literature mentionsJava toolset for working with next generation sequencing data in the BAM format.
View all literature mentionsSoftware tool to enable biologists without training in computer vision or programming to quantitatively measure phenotypes from thousands of images automatically. It counts cells and also measures the size, shape, intensity and texture of every cell (and every labeled subcellular compartment) in every image. It was designed for high throughput screening but can perform automated image analysis for images from time-lapse movies and low-throughput experiments. CellProfiler has an increasing number of algorithms to identify and measure properties of neuronal cell types.
View all literature mentionsSoftware package for high-performance read alignment, quantification and mutation discovery.General purpose read aligner which can be used to map both genomic DNA-seq reads and RNA-seq reads. Subread aligner as fast, accurate and scalable read mapping by seed-and-vote.These programs were also implemented in Bioconductor R package Rsubread.
View all literature mentionsSoftware tool to automate quality and adapter trimming as well as quality control, with some added functionality to remove biased methylation positions for RRBS sequence files for directional, non-directional or paired-end sequencing. Wrapper around Cutadapt and FastQC to consistently apply adapter and quality trimming to FastQ files, with extra functionality for Reduced Representation Bisulfite Sequencing data.
View all literature mentionsA generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms.
View all literature mentionsCompute differentially bound sites from multiple ChIP-seq experiments using affinity (quantitative) data. Also enables occupancy (overlap) analysis and plotting functions.
View all literature mentionsUltrafast and memory efficient tool for aligning sequencing reads to long reference sequences. Supports gapped, local, and paired end alignment modes. More suited to finding longer, gapped alignments in comparison with original Bowtie method.
View all literature mentionsSoftware package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.
View all literature mentionsTo create stitched enhancers, and to separate super enhancers from typical enhancers using sequencing data given file of previously identified constituent enhancers .
View all literature mentionsThis monoclonal targets Ki-67
View all literature mentionsThis monoclonal targets Tubulin, beta
View all literature mentionsThis polyclonal targets Histone H3.3, K27M mutant
View all literature mentionsThis monoclonal targets Synapsin I/II/III
View all literature mentionsThis monoclonal targets BrdU (Bu20a) Mouse mAb
View all literature mentionsThis monoclonal targets NPTX2
View all literature mentionsThis polyclonal targets Histone H3, trimethyl (Lys27)
View all literature mentionsThis polyclonal targets H3K4me1
View all literature mentionsThis unknown targets H3K27ac
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Mus musculus with name NOD.Cg-Prkdcscid Il2rg
Cell line BJ [Human fibroblast] is a Finite cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SU-DIPG-IV is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SU-DIPG-XIII is a Cancer cell line with a species of origin Homo sapiens (Human)
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