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Series GSE95781 Query DataSets for GSE95781
Status Public on Oct 02, 2017
Title Histone H3K4 monomethylation catalyzed by Trr and mammalian COMPASS-like proteins at enhancers is dispensable for development and viability
Organisms Drosophila melanogaster; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Histone H3 lysine 4 monomethylation (H3K4me1) is an evolutionarily conserved feature of enhancer chromatin catalyzed by the COMPASS-like methyltransferase family that includes Trr in Drosophila melanogaster and MLL3 (encoded by KMT2C) and MLL4 (encoded by KMT2D) in mammals. Here we demonstrate that Drosophila embryos expressing catalytically deficient Trr eclose and develop to productive adulthood. Parallel experiments with a trr allele that augments enzyme product specificity show that conversion of H3K4me1 at enhancers to H3K4me2 and H3K4me3 is also compatible with life and results in minimal changes in gene expression. Similarly, loss of the catalytic SET domains of MLL3 and MLL4 in mouse embryonic stem cells (mESCs) does not disrupt selfrenewal. Drosophila embryos with trr alleles encoding catalytic mutants manifest subtle developmental abnormalities when subjected to temperature stress or altered cohesin levels. Collectively, our findings suggest that animal development can occur in the context of Trr or mammalian COMPASS-like proteins deficient in H3K4 monomethylation activity and point to a possible role for H3K4me1 on cis-regulatory elements in specific settings to fine-tune transcriptional regulation in response to environmental stress.
 
Overall design ChIP-seq and RNA-seq experiments were conducted in Drosophila wing imaginal discs and adult brain tissues from transgenic flies expressing either a catalytic-deficient (Trr-C2398A) or catalytic-hyperactive (Trr-Y2383F) Trr enzyme. ChIP-seq and RNA-seq were also conducted in mouse embryonic stem cells in which CRISPR-Cas9 was used to delete the SET domain of both MLL3 and MLL4 (MLL3/4-delSET).
 
Contributor(s) Rickels RA, Collings CK, Shilatifard A
Citation(s) 28967912
Submission date Mar 07, 2017
Last update date Jul 25, 2021
Contact name Ali Shilatifard
E-mail(s) ash@northwestern.edu
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)
GPL19132 Illumina NextSeq 500 (Drosophila melanogaster)
Samples (93)
GSM2525765 dm3.brains.RNAseq.ca.rep1
GSM2525766 dm3.brains.RNAseq.ca.rep2
GSM2525767 dm3.brains.RNAseq.wt.rep1
Relations
BioProject PRJNA378409
SRA SRP101507

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE95781_RAW.tar 14.8 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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