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Series GSE181950 Query DataSets for GSE181950
Status Public on Aug 11, 2022
Title H3K4 Methylation in β-cells prevents transcriptional downregulation and variance associated with type 2 diabetes [RNA-seq]
Organisms Drosophila melanogaster; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Insufficient insulin release by β-cells is the primary etiology in type 2 diabetes (T2D) and coincides with impaired expression of genes essential to β-cell function, but drivers of gene expression dysregulation are not well resolved. We find that H3K4me3 peak breadth correlates with gene expression dysregulation in T2D. Using an adult β-cell Dpy30-KO mouse model, we show that global reduction of H3K4 methylation causes downregulation of genes also downregulated in T2D. Reduction of H3K4 methylation increases transcriptional entropy and reduces insulin production and glucose-responsiveness. Depletion of H3K4 methylation causes global dilution of epigenetic complexity but does not generally reduce gene expression – instead, genes related to β-cell function and/or in particular chromatin environments are specifically affected. Our data further suggests that promoter-associated H3K4me1 is sufficient to maintain expression in the absence of H3K4me3. These data implicate dysregulation of H3K4 methylation in destabilizing gene expression and contributing to β-cell dysfunction in T2D.
 
Overall design RNA-seq of 3 replicates at 2 time points, scRNA-seq of 1 replicate at 1 time point, from Dpy30-KO or CTRL mouse beta cells
Please note that the "scRNAseq_commands.txt" contains the processing pipeline details to regenerate the processed data from raw data for scRNA-seq. The file "mtmg_long.fa" containing egfp and tdtomato sequences is necessary to regenerate the processed data.
 
Contributor(s) Vanderkruk B, Maeshima N, Pasula DJ, An M, Suresh P, Daniel A, McDonald CL, Luciani DS, Hoffman BG
Citation(s) 36912927
Submission date Aug 12, 2021
Last update date Aug 04, 2023
Contact name Brad Hoffman
E-mail(s) brad.hoffman@ubc.ca
Organization name University of British Columbia
Street address Room A4-151 950 W28 Ave
City Vancouver
State/province BC
ZIP/Postal code V5Z 2B3
Country Canada
 
Platforms (2)
GPL19057 Illumina NextSeq 500 (Mus musculus)
GPL25537 Illumina NextSeq 500 (Drosophila melanogaster; Mus musculus)
Samples (14)
GSM5514728 Day 15 RNA-seq WT 1
GSM5514729 Day 15 RNA-seq WT 2
GSM5514730 Day 15 RNA-seq WT 3
This SubSeries is part of SuperSeries:
GSE181951 H3K4 Methylation in β-cells prevents transcriptional downregulation and variance associated with type 2 diabetes.
Relations
BioProject PRJNA754034
SRA SRP332227

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
GSE181950_LFC_D15.csv.gz 717.1 Kb (ftp)(http) CSV
GSE181950_LFC_D45.csv.gz 766.7 Kb (ftp)(http) CSV
GSE181950_RAW.tar 37.3 Mb (http)(custom) TAR (of MTX)
GSE181950_geneCounts.csv.gz 1.1 Mb (ftp)(http) CSV
GSE181950_mtmg_long.fa.gz 950 b (ftp)(http) FA
GSE181950_scRNAseq_commands.txt.gz 885 b (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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