Repression of gene expression by unphosphorylated NF-κB p65 through epigenetic mechanisms

• DOI: 10.1101/gad.1657408
• Publication Date: 2008-04-12T01:07:33Z
• Authors: Jie Dong; Eijiro Jimi; Haihong Zhong; Matthew S. Hayden; Sankar Ghosh
• Keywords: Transcription

Cells from a “knock-in” mouse expressing NF-κB p65 mutant bearing an alanine instead of serine at position 276 (S276A) display significant reduction NF-κB-dependent transcription, even though the forms appropriate complexes that translocate normally to nucleus and bind DNA. Surprisingly, however, expected embryonic lethality hepatocyte apoptosis seen in absence activity, S276A knock-in embryos die different days due variegated developmental abnormalities. We now demonstrate this phenotype is epigenetic repression resulting recruitment histone deacetylases by nonphosphorylatable form into vicinity genes positioned fortuitously near NF-κB-binding sites. Therefore, unphosphorylated nuclear can affect expression not regulated through mechanisms.