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-κB (NF-κB), 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-α 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-κB-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.
Original language | English (US) |
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Pages (from-to) | 291-296 |
Number of pages | 6 |
Journal | EMBO reports |
Volume | 7 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2006 |
Keywords
- Chromatin
- Histone deacetylases
- IKK2
- NF-kB
- TNF-α
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Genetics