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The lineage-specific transcription factor (TF) MEF2C is often deregulated in leukemia. However, strategies to target this TF have yet to be identified. Here, we used a domain-focused CRISPR screen to reveal an essential role for LKB1 and its Salt-Inducible Kinase effectors (SIK3, in a partially redundant manner with SIK2) to maintain MEF2C function in acute myeloid leukemia (AML). A key phosphorylation substrate of SIK3 in this context is HDAC4, a repressive cofactor of MEF2C. Consequently, targeting of LKB1 or SIK3 diminishes histone acetylation at MEF2C-bound enhancers and deprives leukemia cells of the output of this essential TF. We also found that MEF2C-dependent leukemias are sensitive to on-target chemical inhibition of SIK activity. This study reveals a chemical strategy to block MEF2C function in AML, highlighting how an oncogenic TF can be disabled by targeting of upstream kinases.
Pubmed ID: 29526696 RIS Download
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Software ultrafast memory efficient tool for aligning sequencing reads. Bowtie is short read aligner.
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis monoclonal targets Phospho-PKA Substrate (RRXS*/T*)
View all literature mentionsThis polyclonal targets H3K27ac
View all literature mentionsThis monoclonal targets Phospho-HDAC4 (Ser246)/HDAC5 (Ser259)/HDAC7 (Ser155)
View all literature mentionsThis monoclonal targets MEF2C (D80C1) XP Rabbit mAb
View all literature mentionsThis monoclonal targets LKB1 (D60C5) Rabbit mAb
View all literature mentionsThis polyclonal targets SIK3
View all literature mentionsThis monoclonal targets HSC 70 (B-6)
View all literature mentionsSoftware tool for transcriptome assembly and differential expression analysis for RNA-Seq. Includes script called cuffmerge that can be used to merge together several Cufflinks assemblies. It also handles running Cuffcompare as well as automatically filtering a number of transfrags that are likely to be artifacts. If the researcher has a reference GTF file, the researcher can provide it to the script to more effectively merge novel isoforms and maximize overall assembly quality.
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 mentionsSoftware tools for Motif Discovery and next-gen sequencing analysis. Used for analyzing ChIP-Seq, GRO-Seq, RNA-Seq, DNase-Seq, Hi-C and numerous other types of functional genomics sequencing data sets. Collection of command line programs for unix style operating systems written in Perl and C++.
View all literature mentionsWeb service to analyze gene or protein lists. Provides automated meta analysis tools to understand pathways within a group of orthogonal target-discovery studies.
View all literature mentionsPortal to interactively visualize genomic data. Provides reference sequences and working draft assemblies for collection of genomes and access to ENCODE and Neanderthal projects. Includes collection of vertebrate and model organism assemblies and annotations, along with suite of tools for viewing, analyzing and downloading data.
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 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 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 mentionsCell line NIH 3T3 is a Spontaneously immortalized cell line with a species of origin Mus musculus
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line RD is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SNU-423 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SNU-387 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SNU-475 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SNU-449 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Hep 3B2.1-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Hep-G2 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MIA PaCa-2 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line BxPC-3 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line CFPAC-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line AsPC-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H82 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H526 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H446 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line DMS 114 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line K-562 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U-937 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEL 92.1.7 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line THP-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MV4-11 is a Cancer cell line with a species of origin Homo sapiens (Human)
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