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Tumour necrosis factor-alpha depletes histone deacetylase 1 protein through IKK2.

ABSTRACT: Class I histone deacetylases (HDACs) are ubiquitous enzymes that repress gene expression by deacetylating histone tails and promoting chromatin compaction. Pro-inflammatory agents activate programmes of gene expression through transcription factors such as nuclear factor-kappaB (NF-kappaB), even in the context of ubiquitous HDAC activity. How this is accomplished remains unknown. We found that cells treated with the pro-inflammatory cytokine tumour necrosis factor-alpha rapidly and substantially reduced HDAC1 protein levels without affecting other class I HDACs. In addition, HDAC1 depletion occurred through protein degradation, required IKK2 activity and resulted in increased transcription from both NF-kappaB-associated and unassociated gene promoters. Our study suggests that the activation of programmes of gene expression by pro-inflammatory agents requires global changes in specific critical epigenetic regulators such as HDAC1.

SUBMITTER: Vashisht Gopal YN

PROVIDER: S-EPMC1456891 | biostudies-other | 2006 Mar

REPOSITORIES: biostudies-other

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Tumour necrosis factor-alpha depletes histone deacetylase 1 protein through IKK2.

Vashisht Gopal Y N YN Arora Tarandeep S TS Van Dyke Michael W MW

EMBO reports 20051223 3

Class I histone deacetylases (HDACs) are ubiquitous enzymes that repress gene expression by deacetylating histone tails and promoting chromatin compaction. Pro-inflammatory agents activate programmes of gene expression through transcription factors such as nuclear factor-kappaB (NF-kappaB), even in the context of ubiquitous HDAC activity. How this is accomplished remains unknown. We found that cells treated with the pro-inflammatory cytokine tumour necrosis factor-alpha rapidly and substantially ...[more]

PMID: 16374504

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Project description:BackgroundThe humoral system is activated and various cytokines are released due to infections in tissues and traumatic damage. Nuclear factor-kappa B dimers are encoded by nuclear factor-kappa B genes and regulate transcription of several crucial proteins of inflammation such as tumour necrosis factor-alpha.AimsTo investigate the possible effect of polymorphisms on tumour necrosis factor-alpha serum levels with clinical and prognostic parameters of sepsis by determining the nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A) gene polymorphisms and tumour necrosis factor-alpha serum levels.Study designCase-control study.MethodsSeventy-two patients with sepsis and 104 healthy controls were included in the study. In order to determine the polymorphisms of nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A), polymerase chain reaction-restriction fragment length polymorphism analysis was performed and serum tumour necrosis factor-alpha levels were determined using an enzyme-linked immunosorbent assay.ResultsWe observed no significant differences in tumour necrosis factor-alpha serum levels between the study groups. In the patient group, an increase in the tumour necrosis factor-alpha serum levels in patients carrying the tumour necrosis factor-alpha (-308 G/A) A allele compared to those without the A allele was found to be statistically significant. Additionally, an increase in the tumour necrosis factor-alpha serum levels in patients carrying tumour necrosis factor-alpha (-308 G/A) AA genotype compared with patients carrying the AG or GG genotypes was statistically significant. No significant differences were found in these 2 polymorphisms between the patient and control groups (p>0.05).ConclusionOur results showed the AA genotype and the A allele of the tumour necrosis factor-alpha (-308 G/A) polymorphism may be used as a predictor of elevated tumour necrosis factor-alpha levels in patients with sepsis.

Dataset Information

Tumour necrosis factor-alpha depletes histone deacetylase 1 protein through IKK2.

Publications

Tumour necrosis factor-alpha depletes histone deacetylase 1 protein through IKK2.

Similar Datasets

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