title: Histone acetyltransferase HBO1 inhibits NF-kappaB activity by coactivator sequestration.
abstract: 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.
authors.affiliation: Laboratory of Cutaneous Biology, CHUV, Service of Dermatology, Hospital Beaumont 04-421, Lausanne 1011, Switzerland.
authors.forename: Romuald
authors.initials: R
authors.lastname: Contzler
authors.forename: Alexander
authors.initials: A
authors.lastname: Regamey
authors.forename: Bertrand
authors.initials: B
authors.lastname: Favre
authors.forename: Thierry
authors.initials: T
authors.lastname: Roger
authors.forename: Daniel
authors.initials: D
authors.lastname: Hohl
authors.forename: Marcel
authors.initials: M
authors.lastname: Huber
mesh_terms: 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
chemical_list: D016328:NF-kappa B; D011944:Receptors, Androgen; D014409:Tumor Necrosis Factor-alpha; D051548:Histone Acetyltransferases