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EMBO Rep. 2006 Mar;7(3):291-6. Epub 2005 Dec 23.

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

Author information

1
Department of Molecular and Cellular Oncology, Unit 079, UT M.D. Anderson Cancer Center, Houston, Texas 77030-4009, USA.

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.

PMID:
16374504
PMCID:
PMC1456891
DOI:
10.1038/sj.embor.7400613
[Indexed for MEDLINE]
Free PMC Article

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