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Series GSE125203 Query DataSets for GSE125203
Status Public on Feb 26, 2019
Title Chromatin accessibility landscape upon induction of Msgn1, Pax3 and Myf5 in mesodermal cells and identification of conserved Pax3 binding sites and target genes during skeletal myogenesis
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary The transcriptional mechanisms driving lineage specification during development are still largely unknown as the interplay of multiple transcription factors makes it difficult to dissect these molecular events. Using a cell-based differentiation platform to probe transcription function, we investigated the role of the key paraxial mesoderm and skeletal myogenic commitment factors, Msgn1, Tbx6, Foxc1, Pax3, Paraxis, Meox1, Six1 and Myf5, in paraxial mesoderm and skeletal myogenesis. From this study, we define a genetic hierarchy, with Pax3 emerging as the gatekeeper between the presomitic mesoderm and the myogenic lineage. By assaying chromatin accessibility, genomic binding and transcription profiling in mesodermal cells from mouse and human Pax3-induced embryonic stem cells and Pax3-null E9.5 mouse embryos, we identified conserved Pax3 functions in the activation of the skeletal myogenic lineage through modulation of Hedgehog, Notch, and BMP signaling pathways. In addition, we demonstrate that Pax3 molecular function involves chromatin remodeling of its bound elements through an increase in chromatin accessibility and cooperation with Six4 and Tead2 factors. Together, our data provide the first integrated analysis of Pax3 function, demonstrating its ability to remodel chromatin in mesodermal cells from developing embryos and proving a mechanistic footing for the transcriptional hierarchy driving myogenesis.
Overall design Pax3, Msgn1 and Myf5 function during mesoderm specification was investigated using doxycycline-inducible embryonic stem (ES) cells. ATAC-seq was used to identify changes in chromatin accessibility induced by Msgn1, Pax3 and Myf5 upon 1-day induction in serum and serum-free differentiation media. In addition, Pax3-induced changes in chromatin accessibility were investigated also when Pax3 was expressed in NIH3T3 fibroblasts. ChIP-seq was used to determine Pax3 genomic occupancy in mouse ES cells undergoing myogenic specification (1-day and 6-day induction), human differentiating ES cells (1-day induction) and in mouse NIH3T3 fibroblasts (1-day induction). Gene expression changes induced by Pax3 in mouse (1-day and 6-day induction) and human (1-day induction) differentiating ES cells were assessed by RNA-seq.
Contributor(s) Magli A, Perlingeiro RC, Swanson SA
Citation(s) 30807574
Submission date Jan 16, 2019
Last update date Mar 27, 2019
Contact name Alessandro Magli
Organization name University of Minnesota
Department Medicine
Street address 2231 6th St SE
City Minneapolis
State/province MN
ZIP/Postal code 55455
Country USA
Platforms (4)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL21626 NextSeq 550 (Mus musculus)
Samples (65)
GSM3565059 ATACseq_Pax3_wt_embryo_rep1
GSM3565060 ATACseq_Pax3_ko_embryo_rep1
GSM3565061 ATACseq_Pax3_ko_embryo_rep2
BioProject PRJNA515516
SRA SRP179773

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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
GSE125203_ATAC_peaks.tar.gz 12.9 Mb (ftp)(http) TAR
GSE125203_ChIP_peaks.tar.gz 1.5 Mb (ftp)(http) TAR
GSE125203_RAW.tar 1.1 Mb (http)(custom) TAR (of BED)
GSE125203_RNAseq_human_iPAX3_1day.xlsx 1.2 Mb (ftp)(http) XLSX
GSE125203_RNAseq_mouse_iPax3_1day_6day.xlsx 2.0 Mb (ftp)(http) XLSX
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