Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

P300 and CBP are essential for skeletal muscle homeostasis, contractile function and survival

ABSTRACT: Reversible ε-amino acetylation of lysine residues regulates transcription as well as metabolic flux; however, roles for specific lysine acetyltransferases in skeletal muscle physiology and function is unknown. In this study, we investigated the role of the related acetyltransferases p300 and CBP in skeletal muscle transcriptional homeostasis and physiology in adult mice. These data reveal that p300 and CBP are required for the control and maintenance of contractile function and transcriptional homeostasis in skeletal muscle, and ultimately, organism survival.

ORGANISM(S): Mus musculus

PROVIDER: GSE141857 | GEO | 2019/12/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

p300 and CBP are essential for skeletal muscle homeostasis, contractile function and survival

Project 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.

2020-04-03 | PXD015694 | Pride

p300 and CBP are essential for skeletal muscle homeostasis, contractile function and survival

Project description:p300 and CBP are essential for skeletal muscle homeostasis, contractile function and survival

| PRJNA594968 | ENA

Time-resolved analysis reveals rapid dynamics and broad scope of the CBP/p300 acetylome

Project description:The acetyltransferases CBP and p300 are multifunctional transcriptional co-activators; however, their acetylation targets, site-specific acetylation kinetics, and function in proteome regulation are incompletely understood. We combined quantitative proteomics with novel CBP/p300-specific catalytic inhibitors, bromodomain inhibitor, and gene knockout to show that CBP/p300 acetylates thousands of sites, including signature histone sites, as well as a multitude of sites on signaling effectors and enhancer-associated transcriptional regulators. Kinetic analysis identified a subset of CBP/p300-regulated sites with very rapid (<30min) acetylation turnover, revealing a dynamic balance between acetylation and deacetylation. Quantification of acetylation, mRNA, and protein abundance after CBP/p300 inhibition reveals a kinetically competent network of gene expression that strictly depends on CBP/p300-catalyzed rapid acetylation. Collectively, our in-depth acetylome analyses reveal systems attributes of CBP/p300 targets, and the resource dataset provides a framework for investigating CBP/p300 functions, as well as for understanding the impact of small molecule inhibitors targeting its catalytic and bromodomain activities.

2018-06-10 | PXD005252 | Pride

Expression data from wild type and CBP/p300 null MEFs +/- 3hr treatment with 100uM dipyridyl (DP)

Project description:Genome-wide distribution of histone H3K18 and H3K27 acetyltransferases, Crebbp (CBP) and Ep300 (p300), is used to map enhancers and promoters, but whether these elements functionally require CBP/p300 remains largely uncertain. We investigated this relationship by comparing genomic CBP recruitment with gene expression in wild type and CBP/p300 double-knockout fibroblasts. ChIP-seq revealed nearby CBP recruitment for 20 percent of constitutively expressed genes, but surprisingly, three-quarters of these were unaffected or slightly activated by CBP/p300 deletion. Computationally defined enhancer-promoter-units (EPUs) having a CBP peak within two kilobases of the enhancer-like element provided better predictive value, with CBP/p300 deletion attenuating expression of 40 percent of such EPU assigned constitutively expressed genes. We next examined signaling-responsive (Hypoxia Inducible Factor) gene expression and CBP recruitment, and found that 97 percent of inducible genes were within 50 kilobases of an inducible CBP peak, and 70 percent of these required CBP/p300 for full inducible expression. Unexpectedly however, most inducible CBP peaks occurred near signal-nonresponsive genes. 12 samples, 3 each wild type and CBP/p300 null treated for 3hrs with 100uM dipyridyl orethanol vehicle.

2014-09-29 | E-GEOD-54452 | biostudies-arrayexpress

Targeting P300/CBP reveals discrete regulation of transcription and chromatin accessibility by histone acetylation [Hi-C]

Project description:To test the long-standing paradigm directly linking histone acetylation with chromatin decompaction and transcriptional output, we used integrated epigenomic and transcriptomic analyses following acute inhibition of major cellular lysine acetyltransferases P300 and CBP. We discovered that P300/CBP inhibition dynamically perturbs acetylation kinetics and dramatically suppresses core-transcriptional networks in the absence of changes to chromatin accessibility. CRISPR/Cas9 screening identified NCOR1 and HDAC3 transcriptional co-repressors as the principle antagonists of P300/CBP by counteracting acetylation turnover kinetics. Finally, deacetylation of H3K27 provides nucleation sites for reciprocal methylation switching, a feature that can be exploited therapeutically by concomitant KDM6A and P300 inhibition. Overall, this study indicates that the steady-state histone acetylation-methylation equilibrium functions as a molecular rheostat governing cellular transcription that is amenable to therapeutic exploitation as an anti-cancer regimen.

2021-05-11 | GSE173781 | GEO

Targeting P300/CBP reveals discrete regulation of transcription and chromatin accessibility by histone acetylation [CRISPR]

2021-05-11 | GSE173772 | GEO

Targeting P300/CBP reveals discrete regulation of transcription and chromatin accessibility by histone acetylation [singlecellseq]

2021-05-11 | GSE173811 | GEO

Targeting P300/CBP reveals discrete regulation of transcription and chromatin accessibility by histone acetylation [PRO-seq]

2021-05-11 | GSE173783 | GEO

Targeting P300/CBP reveals discrete regulation of transcription and chromatin accessibility by histone acetylation [ChIPseq]

2021-05-11 | GSE173775 | GEO

Targeting P300/CBP reveals discrete regulation of transcription and chromatin accessibility by histone acetylation [RNAseq]

2021-05-11 | GSE174266 | GEO