GSE77108: HDAC inhibitor SAHA reverses inflammatory gene expression in diabetic endothelial cells

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GROUP CONDITION SAMPLES
Human aortic endothelial cell
GSM2044443 GSM2044444 GSM2044445
GSM2044431 GSM2044432 GSM2044433
GSM2044437 GSM2044438 GSM2044439
GSM2044428 GSM2044429 GSM2044430
GSM2044440 GSM2044441 GSM2044442
GSM2044434 GSM2044435 GSM2044436
GSM2044419 GSM2044420 GSM2044421
GSM2044422 GSM2044423 GSM2044424
GSM2044446 GSM2044447 GSM2044448
GSM2044425 GSM2044426 GSM2044427
Description

Submission Date: Jan 21, 2016

Summary: While histone deacetylase (HDAC) inhibitors are thought to regulate gene expression by post-translational modification of histone as well as non-histone proteins. While histone hyperacetylation has long been considered the paradigmatic mechanism of action, recent genome-wide profiles indicate more complex interactions with the epigenome. In particular, HDAC inhibitors also induce histone deacetylation at the promoters of highly active genes, resulting in gene suppression. This was linked to the loss of histone acetyltransferase (HAT) binding. To illustrate pre-clinical utility of the HDAC inhibitor SAHA as a therapeutic, we show reversal of diabetes-associated EP300 target genes in diabetic HAECs of primary origin. These results were confirmed using SAHA, C646 (EP300/CREBBP inhibitor) or EP300 siRNA. These findings suggest the inhibition of gene expression by SAHA is mediated by EP300 function and provide a rationale for clinical trials of safety and efficacy in patients with diabetes.

GEO Accession ID: GSE77108

PMID: 28886276

Description

Submission Date: Jan 21, 2016

Summary: While histone deacetylase (HDAC) inhibitors are thought to regulate gene expression by post-translational modification of histone as well as non-histone proteins. While histone hyperacetylation has long been considered the paradigmatic mechanism of action, recent genome-wide profiles indicate more complex interactions with the epigenome. In particular, HDAC inhibitors also induce histone deacetylation at the promoters of highly active genes, resulting in gene suppression. This was linked to the loss of histone acetyltransferase (HAT) binding. To illustrate pre-clinical utility of the HDAC inhibitor SAHA as a therapeutic, we show reversal of diabetes-associated EP300 target genes in diabetic HAECs of primary origin. These results were confirmed using SAHA, C646 (EP300/CREBBP inhibitor) or EP300 siRNA. These findings suggest the inhibition of gene expression by SAHA is mediated by EP300 function and provide a rationale for clinical trials of safety and efficacy in patients with diabetes.

GEO Accession ID: GSE77108

PMID: 28886276

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