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PXD015694

PXD015694 is an original dataset announced via ProteomeXchange.

Dataset Summary
Titlep300 and CBP are essential for skeletal muscle homeostasis, contractile function and survival
DescriptionReversible epsilon-amino acetylation of lysine residues regulates transcription as well as metabolic flux; however, roles for specific lysine acetyltransferases in skeletal muscle physiology and function remain enigmatic. In this study, we investigated the role of the homologous acetyltransferases p300 and CBP in skeletal muscle transcriptional homeostasis and physiology in adult mice. Mice with skeletal muscle-specific and inducible knockout of p300 and/or CBP were generated by crossing mice with a tamoxifen-inducible Cre recombinase expressed under the human alpha-skeletal actin (HSA) promoter with mice harboring LoxP sites flanking exon 9 of both the Ep300 and Crebbp genes. Knockout was induced at 13-15 weeks of age via oral gavage of tamoxifen. We demonstrate that loss of both p300 and CBP in adult mouse skeletal muscle severely impairs contractile function and results in lethality within one week – a phenotype that is reversed by the presence of a single allele of either p300 or CBP. The loss of muscle function in p300/CBP double knockout mice is paralleled by substantial transcriptional alterations in gene networks central to skeletal muscle contraction and structural integrity. Changes in protein expression patterns, determined by 10-plex TMT labeling, were linked to impaired muscle function also manifest within days (WT mice were compared to day 3 and day 5 knock out mice). Together, these data reveal the requirement of p300 and CBP for the control and maintenance of contractile function and transcriptional homeostasis in skeletal muscle, and ultimately, organism survival. By extension, modulating p300/CBP function holds promise for the treatment of disorders characterized by impaired contractile function in humans.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:01:37.623.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterPhillip Wilmarth
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion ETD
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-10-04 01:17:56ID requested
12020-04-02 23:09:51announced
22024-10-22 05:01:45announced2024-10-22: Updated project metadata.
Publication List
10.1002/jcsm.12522;
Svensson K, LaBarge SA, Sathe A, Martins VF, Tahvilian S, Cunliffe JM, Sasik R, Mahata SK, Meyer GA, Philp A, David LL, Ward SR, McCurdy CE, Aslan JE, Schenk S, p300 and cAMP response element-binding protein-binding protein in skeletal muscle homeostasis, contractile function, and survival. J Cachexia Sarcopenia Muscle, 11(2):464-477(2020) [pubmed]
Keyword List
submitter keyword: proteomics, muscle contraction, acetyltransferases,Acetylation, transcriptomics
Contact List
Dr. Simon Schenk
contact affiliationDepartment of Orthopaedic Surgery School of Medicine University of California San Diego 9500 Gilman Drive MC0863 La Jolla, CA, USA
contact emailsschenk@ucsd.edu
lab head
Phillip Wilmarth
contact affiliationOHSU
contact emailwilmarth@ohsu.edu
dataset submitter
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Dataset FTP location
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