Acetylation of p65 at lysine 314 is important for late NF-kappaB-dependent gene expression.
BACKGROUND
NF-kappaB regulates the expression of a large number of target genes involved in the immune and inflammatory response, apoptosis, cell proliferation, differentiation and survival. We have earlier reported that p65, a subunit of NF-kappaB, is acetylated in vitro and in vivo at three different lysines (K310, K314 and K315) by the histone acetyltransferase p300.


RESULTS
In this study, we describe that site-specific mutation of p65 at lysines 314 and 315 enhances gene expression of a subset of NF-kappaB target genes including Mmp10 and Mmp13. Increased gene expression was mainly observed three hours after TNFalpha stimulation. Chromatin immunoprecipitation (ChIP) experiments with an antibody raised against acetylated lysine 314 revealed that chromatin-bound p65 is indeed acetylated at lysine 314.


CONCLUSIONS
Together, our results establish acetylation of K314 as an important regulatory modification of p65 and subsequently of NF-kappaB-dependent gene expression.
Rothgiesser
Karin M
KM
Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Fey
Monika
M
Hottiger
Michael O
MO
D000107:Acetylation; D000818:Animals; D047369:Chromatin Immunoprecipitation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008239:Lysine / Q000235:genetics; D053506:Matrix Metalloproteinase 10 / Q000235:genetics; D053509:Matrix Metalloproteinase 13 / Q000235:genetics; D051379:Mice; D009154:Mutation; D041681:NIH 3T3 Cells; D020411:Oligonucleotide Array Sequence Analysis; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000235:genetics; D051996:Transcription Factor RelA / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha
D011994:Recombinant Proteins; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D053509:Matrix Metalloproteinase 13; D053506:Matrix Metalloproteinase 10; D008239:Lysine