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Series GSE129037 Query DataSets for GSE129037
Status Public on Mar 17, 2020
Title Uncoupling histone H3K4 trimethylation from developmental gene expression via an epigenetic equilibrium of Polycomb, COMPASS and DNA methylation
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
Summary The COMPASS family catalyzes histone H3 lysine 4 (H3K4) methylation and its members are essential for regulating developmental gene expression. MLL2/COMPASS methylates H3K4 on many genes but only a subset lose expression upon MLL2 loss. To understand MLL2 -dependent transcriptional regulation, we performed a CRISPR screen in mouse embryonic stem cells (mESCs) and found that MLL2 protects developmental genes from repression by repelling PRC2 and DNA methylation machineries from these loci. Repression in the absence of MLL2 is relieved by inhibition of PRC2 and DNA methyltransferases, demonstrating that prevention of active repression and not H3K4me3 underlies their transcriptional state. DNA demethylation on such loci leads to reactivation of MLL2-dependent genes not only by removing DNA methylation but also by opening up previously CpG methylated regions for PRC2 recruitment, diluting PRC2 at Polycomb-repressed genes. These findings reveal how the context and function of these three epigenetic modifiers can orchestrate transcriptional decisions.
Overall design CRISPR screen for regulators of MagohB expression followed ChIP-seq, RNAseq, PRO-seq and bisulfite sequencing analyses of selected candidates and their regulators
Contributor(s) Douillet D, Bartom E, Shilatifard A
Citation(s) 32393859
Submission date Mar 29, 2019
Last update date Jun 16, 2020
Contact name Ali Shilatifard
Organization name Northwestern University Feinberg School of Medicine
Department Department of Biochemistry and Molecular Genetics
Lab Shilatifard Lab
Street address 320 E Superior St
City Chicago
State/province IL
ZIP/Postal code 60611
Country USA
Platforms (2)
GPL19057 Illumina NextSeq 500 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (128)
GSM3692066 mES_WT_Mll2ChIP_rep1
GSM3692067 mES_Mll2KO_Mll2ChIP_rep1
GSM3692068 mES_input_Mll2ChIP_rep1
BioProject PRJNA529856
SRA SRP189864

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Supplementary file Size Download File type/resource
GSE129037_RAW.tar 13.9 Gb (http)(custom) TAR (of BW, COV, TXT)
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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