Histone acetyltransferase HBO1 inhibits NF-kappaB activity by coactivator sequestration.
The MYST acetyltransferase HBO1 is implicated in the regulation of DNA replication and activities of transcription factors such as the androgen receptor. Since the androgen receptor and NF-kappaB transcription factors crossmodulate their transcriptional activity, we investigated whether HBO1 regulates NF-kappaB signaling. Here, we report that in 293T cells HBO1 reduced dose-dependently NF-kappaB activity stimulated by TNFalpha, or by overexpressing p65/RelA, RelB, or cRel. Mutational analysis showed that the N-terminal serine-rich region of HBO1 but not the acetyltransferase function was required for inhibition. Electrophoretic mobility-shift assays demonstrated that HBO1 was neither perturbing the formation of p65/RelA DNA complexes nor binding itself to the kappaB consensus sequence or to p65/RelA, suggesting that HBO1 reduced NF-kappaB activity by squelching a cofactor. These data establish a novel function for HBO1 showing that it reduced NF-kappaB activity by sequestrating an essential coactivator from the NF-kappaB transcriptional complex.
Contzler
Romuald
R
Laboratory of Cutaneous Biology, CHUV, Service of Dermatology, Hospital Beaumont 04-421, Lausanne 1011, Switzerland.
Regamey
Alexander
A
Favre
Bertrand
B
Roger
Thierry
T
Hohl
Daniel
D
Huber
Marcel
M
D002460:Cell Line; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016328:NF-kappa B; D011944:Receptors, Androgen; D014409:Tumor Necrosis Factor-alpha; D051548:Histone Acetyltransferases