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Series GSE69968 Query DataSets for GSE69968
Status Public on Mar 22, 2016
Title RNA-Sequencing of primary myoblasts from mice with a satellite cell specific knockout of the histone demthylase UTX/KDM6A
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The KDM6 histone demethylases (UTX/KDM6A and JMJD3/KDM6B) mediate removal of repressive histone H3K27me3 marks to establish transcriptionally permissive chromatin. Loss of UTX in female mice is embryonic lethal. Unexpectedly, male UTX-null mice escape embryonic lethality due to expression of UTY, a paralog lacking H3K27-demethylase activity. This suggests that UTX plays an enzyme-independent role in development, and challenges the need for active H3K27-demethylation in vivo. However, the requirement for active H3K27-demethylation in stem cell-mediated tissue regeneration remains untested. Using an inducible mouse knockout that ablates UTX in satellite cells, we show that active H3K27-demethylation is necessary for muscle regeneration. Indeed, loss of UTX in satellite cells blocks myofiber regeneration in both male and female mice. Furthermore, we demonstrate that UTX mediates muscle regeneration through its H3K27-demethylase activity using a chemical inhibitor, and a demethylase-dead UTX knock-in mouse. Mechanistically, dissection of the muscle regenerative process revealed that UTX is required for expression of the transcription factor Myogenin that drives differentiation of muscle progenitors. Thus, we have identified a critical role for the enzymatic activity of UTX in activating muscle-specific gene expression during myofiber regeneration, revealing for the first time that active H3K27-demethylation has a physiological role in vivo.
Overall design Satellite cells were sorted based on Cre-dependent expression of TdT reporter gene. Sorted UTXmKO or UTX WT satellite cells were then induced to differentiate for 24 hrs. RNA was then isolated and subjected to RNA-Seq analysis.
Contributor(s) Faralli H, Chu A, Dilworth JF
Citation(s) 26999603
Submission date Jun 17, 2015
Last update date May 15, 2019
Contact name Marjorie Brand
Organization name Ottawa Hospital Research Institute
Street address 501 Smyth Road
City Ottawa
State/province Ontario
ZIP/Postal code K1H 8L6
Country Canada
Platforms (2)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (8)
GSM1714210 WT_UTX_Female
GSM1714211 KO_UTX_Female
GSM2039003 Ctrl-KI_UTX_Female_Rep1
BioProject PRJNA287291
SRA SRP059609

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

Supplementary file Size Download File type/resource 316.5 Mb (ftp)(http) BW 346.6 Mb (ftp)(http) BW
GSE69968_RAW.tar 634.3 Mb (http)(custom) TAR (of BW)
GSE69968_WT_vs_KI_Female_genes.fpkm_tracking.txt.gz 1.2 Mb (ftp)(http) TXT
GSE69968_WT_vs_KO_Female_genes.fpkm_tracking.txt.gz 944.1 Kb (ftp)(http) TXT
GSE69968_WT_vs_KO_Male_genes.fpkm_tracking.txt.gz 1.1 Mb (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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