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Global gastrocnemius skeletal muscle transcript data from fasted male Gcn5skm-/- (HSAcre Tg/0 x Gcn5 L2/L2) and Gcn5skm+/+ mice (HSAcre 0/0 x Gcn5 L2/L2) on a chow diet

ABSTRACT: Global gastrocnemius skeletal muscle transcript data from fasted male Gcn5skm-/- (HSAcre Tg/0 x Gcn5 L2/L2) and Gcn5skm+/+ mice (HSAcre 0/0 x Gcn5 L2/L2) on a chow diet

PROVIDER: PRJNA666894 | ENA |

REPOSITORIES: ENA

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Global gastrocnemius skeletal muscle transcript data from fasted male Gcn5skm-/- (HSAcre Tg/0 x Gcn5 L2/L2) and Gcn5skm+/+ mice (HSAcre 0/0 x Gcn5 L2/L2) on a chow diet

Project description:Transcript data from gastrocnemius muscle from fasted-state male muscle-specific General Control of Amino Acid Synthesis Protein 5 knockout mice (Gcn5 skm-/- ) and wild-type mice (Gcn5skm+/+). We used microarrays to detail the effects of muscle-specific loss of GCN5 on the global program of gene expression in gastrocnemius muscle.

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Project description:Histone acetyltransferases (HATs) GCN5/PCAF and CBP/p300 are transcription coactivators. However, how these HATs regulate ligand-induced nuclear receptor target gene expression remains unclear. Here we show in mouse embryonic fibroblasts (MEFs), deletion of GCN5/PCAF specifically eliminates acetylation on H3K9 (H3K9Ac) while deletion of CBP/p300 selectively reduces acetylation on H3K18 and H3K27 (H3K18/27Ac). Treating MEFs with a specific ligand for nuclear receptor PPARdelta induces sequential increases of H3K18/27Ac and H3K9Ac on the promoter of PPARdelta target gene Angptl4, which correlates with a robust ligand-induced Angptl4 expression. Inhibiting transcription elongation blocks ligand-induced H3K9Ac but not H3K18/27Ac on Angptl4 promoter. Finally, we show CBP/p300 and their HAT activities are required, while GCN5/PCAF and H3K9Ac are dispensable, for ligand-induced PPARdelta target gene expression in MEFs. These results highlight the substrate and site specificities of HATs in cells, and suggest that GCN5/PCAF- and CBP/p300-mediated histone acetylations play distinct roles in regulating ligand-induced nuclear receptor target gene expression. PCAF and GCN5 have some redundant function. To identify PCAF/GCN5-regulated genes, immortalized MEFs with PCAF knockout and GCN5 conditional knockout were infected with retroviruses expressing either Cre recombinase or vector alone. We prepared duplicated RNAs from either vector or Cre infected cells (PCAF-/-;GCN5+/- or PCAF-/-;GCN5+/-) and RNAs from either Vector or Cre infected the other independently immortalized cells for 6 affymetrix microarray.

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