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Series GSE93167 Query DataSets for GSE93167
Status Public on Feb 01, 2017
Title Conservation and innovation in the DUX4-family gene network [MMH6 RNA-Seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Facioscapulohumeral dystrophy (FSHD; OMIM #158900, #158901) is caused by mis-expression of the DUX4 transcription factor in skeletal muscle1. Animal models of FSHD are hampered by incomplete knowledge of the conservation of the DUX4 transcriptional program in other species. Despite divergence of their binding motifs, both mouse Dux and human DUX4 activate genes associated with cleavage-stage embryos, including MERV-L and ERVL-MaLR retrotransposons, in mouse and human muscle cells respectively. When expressed in mouse cells, human DUX4 maintained modest activation of cleavage-stage genes driven by conventional promoters, but did not activate MERV-L-promoted genes. These findings indicate that the ancestral DUX4-factor regulated genes characteristic of cleavage-stage embryos driven by conventional promoters, whereas divergence of the DUX4/Dux homeodomains correlates with retrotransposon specificity. These results provide insight into how species balance conservation of a core transcriptional program with innovation at retrotransposon promoters and provide a basis for animal models that recreate the FSHD transcriptome.
Overall design We generated a new RNA-seq dataset in mouse myoblasts and compared them to a published dataset for human DUX4 in human myoblasts (GSE85461; DOI:10.1093/hmg/ddw271). This new dataset (and the dataset we compared to) used a doxycycline-inducible system and a codon-altered transgene. This new datasets reflects three separate cell cultures of a clonal cell line induced with doxycycline for eighteen hours, independently barcoded and sequenced in parallel; doxycycline induction caused expression of MMH in mouse myoblasts. MMH is a chimeric gene whose N-terminus is codon-altered mouse Dux through the mouse Dux homeodomains and its C-terminus is codon-altered human DUX4 starting just after human DUX4's homeodomains. The MMH-chimera maintained the DNA binding domain of Dux and the carboxy-terminal epitopes of DUX4, permitting us to use the same DUX4 antisera to immunoprecipitate the MMH-chimera and DUX4 (see related ChIP-seq dataset). We also generated a matched control dataset by preparing three more cell cultures of this same MMH cell line and harvesting them in parallel at eighteen hours, but not treating with doxycycline.
Contributor(s) Whiddon JL, Langford AT, Wong C, Zhong JW, Tapscott SJ
Citation(s) 28459454
NIH grant(s)
Grant ID Grant title Affiliation Name
R01 AR045203 D4Z4 Coding Transcripts and FSHD FRED HUTCHINSON CANCER RESEARCH CENTER Stephen J Tapscott
Submission date Jan 05, 2017
Last update date May 15, 2019
Contact name Stephen Tapscott
Organization name Fred Hutch Cancer Research Center
Department Human Biology
Lab Tapscott
Street address 1100 Fairview N. Ave
City Seattle
State/province WASHINGTON
ZIP/Postal code 98103
Country USA
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (6)
GSM2445810 Sample_1_MMH6_nodox_rep1
GSM2445811 Sample_2_MMH6_nodox_rep2
GSM2445812 Sample_3_MMH6_nodox_rep3
This SubSeries is part of SuperSeries:
GSE87282 Conservation and innovation in the DUX4-family gene network
BioProject PRJNA360229
SRA SRP096106

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Supplementary file Size Download File type/resource
GSE93167_gene_counts.csv.gz 773.9 Kb (ftp)(http) CSV
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