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

Jie Dong, Eijiro Jimi, Haihong Zhong, Matthew S. Hayden, Sankar Ghosh

研究成果: ジャーナルへの寄稿学術誌査読

114 被引用数 (Scopus)

抄録

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

本文言語英語
ページ(範囲)1159-1173
ページ数15
ジャーナルGenes and Development
22
9
DOI
出版ステータス出版済み - 5月 1 2008
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 遺伝学
  • 発生生物学

フィンガープリント

「Repression of gene expression by unphosphorylated NF-κB p65 through epigenetic mechanisms」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル