PXD015694

PXD015694 is an original dataset announced via ProteomeXchange.

Title	p300 and CBP are essential for skeletal muscle homeostasis, contractile function and survival
Description	Reversible 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:01:37.623.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Phillip Wilmarth
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion ETD

Revision	Datetime	Status	ChangeLog Entry
0	2019-10-04 01:17:56	ID requested
1	2020-04-02 23:09:51	announced
⏵ 2	2024-10-22 05:01:45	announced	2024-10-22: Updated project metadata.

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]

submitter keyword: proteomics, muscle contraction, acetyltransferases,Acetylation, transcriptomics

Dr. Simon Schenk
contact affiliation	Department of Orthopaedic Surgery School of Medicine University of California San Diego 9500 Gilman Drive MC0863 La Jolla, CA, USA
contact email	sschenk@ucsd.edu
lab head
Phillip Wilmarth
contact affiliation	OHSU
contact email	wilmarth@ohsu.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/04/PXD015694

PRIDE project URI

• PRIDE
  1. PXD015694
     1. Label: PRIDE project
     2. Name: p300 and CBP are essential for skeletal muscle homeostasis, contractile function and survival