PXD012789-1

PXD012789 is an original dataset announced via ProteomeXchange.

Title	Dissection of the cellular function of the ZBED6 transcription factor in mouse myoblast cells, IGF2-GGCT Lysate
Description	The transcription factor ZBED6 acts as a repressor of Igf2 and affects directly or indirectly the transcriptional regulation of thousands of genes. Here, we use gene editing in mouse C2C12 myoblasts and show that ZBED6 regulates Igf2 exclusively through its binding site 5′-GGCTCG-3′ in intron 1 of Igf2. Deletion of this motif (Igf2ΔGGCT) or complete ablation of Zbed6 leads to ~20-fold up-regulation of IGF2 protein. Quantitative proteomics revealed an activation of Ras signaling pathway in both Zbed6-/- and Igf2ΔGGCT myoblasts, and a significant enrichment of mitochondrial membrane proteins among proteins showing altered expression in Zbed6-/- myoblasts. Both Zbed6-/- and Igf2ΔGGCT myoblasts showed a faster growth rate and developed myotube hypertrophy. These cells exhibited an increased O2 consumption rate, due to IGF2 up-regulation. Transcriptome analysis revealed ~30% overlap between differentially expressed genes in Zbed6-/- and Igf2ΔGGCT myotubes, with an enrichment of up-regulated genes involved in muscle development. In contrast, ZBED6-overexpression in myoblasts led to cell apoptosis, cell cycle arrest, reduced mitochondrial activities and ceased myoblast differentiation. The similarities in growth and differentiation phenotypes observed in Zbed6-/- and Igf2ΔGGCT myoblasts demonstrates that ZBED6 affects mitochondrial activity and myogenesis largely through its regulation of IGF2 expression. This study suggeststhat the interaction between ZBED6-Igf2 may be a therapeutic target for human diseases where anabolism is impaired.
HostingRepository	PRIDE
AnnounceDate	2020-07-07
AnnouncementXML	Submission_2020-07-06_22:13:44.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mårten Larsson
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	isotope labeled residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion ETD

Revision	Datetime	Status	ChangeLog Entry
0	2019-02-19 05:33:44	ID requested
⏵ 1	2020-07-06 22:13:45	announced
2	2024-10-22 05:08:30	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

curator keyword: Biological

submitter keyword: IGF2, ZBED6, mitochondria, myogenesis, SILAC

Leif Andersson
contact affiliation	Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, SE-751 23 Uppsala, Sweden.
contact email	Leif.Andersson@imbim.uu.se
lab head
Mårten Larsson
contact affiliation	Uppsala University
contact email	Marten.Larsson@imbim.uu.se
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD012789
     1. Label: PRIDE project
     2. Name: Dissection of the cellular function of the ZBED6 transcription factor in mouse myoblast cells, IGF2-GGCT Lysate