Histone acetyltransferase HBO1 inhibits NF-κB 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-kappa B transcription factors crossmodulate their transcriptional activity, we investigated whether HBO1 regulates NF-kappa B signaling. Here, we report that in 293T cells HBO1 reduced dose-dependently NF-kappa B activity stimulated by TNF alpha, 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 kappa B consensus sequence or to p65/RelA, suggesting that HBO1 reduced NF-kappa B activity by squelching a cofactor. These data establish a novel function for HBO1 showing that it reduced NF-kappa B activity by sequestrating an essential coactivator from the NF-kappa B transcriptional complex. (c) 2006 Elsevier Inc. All rights reserved.