Cyclin-dependent kinase 9 (CDK9) promotes transcriptional elongation through RNAPII pause release. We now report that CDK9 is also essential for maintaining gene silencing at heterochromatic loci. Through a live cell drug screen with genetic confirmation, we discovered that CDK9 inhibition reactivates epigenetically silenced genes in cancer, leading to restored tumor suppressor gene expression, cell differentiation, and activation of endogenous retrovirus genes. CDK9 inhibition dephosphorylates the SWI/SNF protein BRG1, which contributes to gene reactivation. By optimization through gene expression, we developed a highly selective CDK9 inhibitor (MC180295, IC50 = 5 nM) that has broad anti-cancer activity in vitro and is effective in in vivo cancer models. Additionally, CDK9 inhibition sensitizes to the immune checkpoint inhibitor α-PD-1 in vivo, making it an excellent target for epigenetic therapy of cancer.
Pubmed ID: 30454645 RIS Download
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Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 23,2023. Software tool developed for ArrayTrack that takes a list of genes and identifies terms in Gene Ontology associated with those genes. GOFFA provides tools to view/access the following: GO term hierarchy, full listing of GO terms annotated with the genes associated with a given term, Fisher's exact test p-value providing the probability of identifying that many genes for a given term by chance alone, and relative enrichment factor (E-value) giving the enrichment of a GO term for genes in the submitted list relative to the frequency of genes assigned to that term from the full set of GOFFA annotated genes for a particular species.
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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 mentionsCollection of data of protein sequence and functional information. Resource for protein sequence and annotation data. Consortium for preservation of the UniProt databases: UniProt Knowledgebase (UniProtKB), UniProt Reference Clusters (UniRef), and UniProt Archive (UniParc), UniProt Proteomes. Collaboration between European Bioinformatics Institute (EMBL-EBI), SIB Swiss Institute of Bioinformatics and Protein Information Resource. Swiss-Prot is a curated subset of UniProtKB.
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View all literature mentionsThis monoclonal targets I-A/I-E
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Mus musculus with name NOD.Cg-Prkdcscid Il2rg
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View all literature mentionsCell line LNCaP clone FGC.10 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HL-60 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCT 116 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SW48 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsA software which acquires and processes data sets, primarily through the Xcalibur system.
View all literature mentionsCommercial organization which provides molecular modelling and cheminformatics software to the pharmaceutical industry.
View all literature mentionsSoftware Python package for identifying transcript factor binding sites. Used to evaluate significance of enriched ChIP regions. Improves spatial resolution of binding sites through combining information of both sequencing tag position and orientation. Can be used for ChIP-Seq data alone, or with control sample with increase of specificity.
View all literature mentionsSoftware package that implements the remove unwanted variation (RUV) methods for the normalization of RNA-Seq read counts between samples.
View all literature mentionsA software program that allows you to easily visualize your next-generation sequencing (NGS) samples at functional genomic regions.
View all literature mentionsBioconductor software package for Empirical analysis of Digital Gene Expression data in R. Used for differential expression analysis of RNA-seq and digital gene expression data with biological replication.
View all literature mentionsSoftware tool for fast and high throughput alignment of shotgun cDNA sequencing reads generated by transcriptomics technologies. Fast splice junction mapper for RNA-Seq reads. Aligns RNA-Seq reads to mammalian-sized genomes using ultra high-throughput short read aligner Bowtie, and then analyzes mapping results to identify splice junctions between exons.TopHat2 is accurate alignment of transcriptomes in presence of insertions, deletions and gene fusions.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 23,2023. Provides an integrated solution for managing, analyzing, and interpreting microarray gene expression data.
View all literature mentionsA web-based software application that enables users to analyze, integrate, and understand data derived from gene expression, microRNA, and SNP microarrays, metabolomics, proteomics, and RNA-Seq experiments, and small-scale experiments that generate gene and chemical lists. Users can search for targeted information on genes, proteins, chemicals, and drugs, and build interactive models of experimental systems. IPA allows exploration of molecular, chemical, gene, protein and miRNA interactions, creation of custom molecular pathways, and the ability to view and modify metabolic, signaling, and toxicological canonical pathways. In addition to the networks and pathways that can be created, IPA can provide multiple layering of additional information, such as drugs, disease genes, expression data, cellular functions and processes, or a researchers own genes or chemicals of interest.
View all literature mentionsCollection of genome-wide transcriptional expression data from cultured human cells treated with bioactive small molecules and simple pattern-matching algorithms. camp aims to enable the discovery of functional connections between drugs, genes and diseases through the transitory feature of common gene-expression changes.
View all literature mentionsBioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.
View all literature mentionsSoftware package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentions
Mus musculus with name NOD.Cg-Prkdcscid Il2rg
Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line DU145 is a Cancer cell line with a species of origin Homo sapiens (Human)
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View all literature mentionsThis unknown targets phospho-serine in a (K/H)SP motif
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View all literature mentionsThis polyclonal targets Phospho-Rb (Ser807/811)
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View all literature mentionsThis monoclonal targets Rb (phospho T826)
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View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsSoftware tool to map bisulfite converted sequence reads and determine cytosine methylation states. Flexible aligner and methylation caller for Bisulfite-Seq applications. Used to map bisulfite treated sequencing reads to genome of interest and perform methylation calls in single step.
View all literature mentionsOriginal SAMTOOLS package has been split into three separate repositories including Samtools, BCFtools and HTSlib. Samtools for manipulating next generation sequencing data used for reading, writing, editing, indexing,viewing nucleotide alignments in SAM,BAM,CRAM format. BCFtools used for reading, writing BCF2,VCF, gVCF files and calling, filtering, summarising SNP and short indel sequence variants. HTSlib used for reading, writing high throughput sequencing data.
View all literature mentionsThis monoclonal targets CDK1 antibody [EPR165]
View all literature mentionsThis monoclonal targets SMARCD1
View all literature mentionsThis polyclonal targets CCNT1
View all literature mentionsThis polyclonal targets Cdk9 (C-20)
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets CD45
View all literature mentionsThis monoclonal targets CD11c
View all literature mentionsThis unknown targets Rat
View all literature mentionsThis monoclonal targets I-A/I-E
View all literature mentionsThis monoclonal targets Mouse CD3 Molecular Complex
View all literature mentionsThis unknown targets Mouse IgG1 kappa Isotype Control FITC Clone MOPC-21
View all literature mentionsA powerful toolset for genome arithmetic allowing one to address common genomics tasks such as finding feature overlaps and computing coverage. Bedtools allows one to intersect, merge, count, complement, and shuffle genomic intervals from multiple files in widely-used genomic file formats such as BAM, BED, GFF/GTF, VCF. While each individual tool is designed to do a relatively simple task (e.g., intersect two interval files), quite sophisticated analyses can be conducted by combining multiple bedtools operations on the UNIX command line.
View all literature mentions