LPS promotes HBO1 stability via USP25 to modulate inflammatory gene transcription in THP-1 cells.

ABSTRACT

The histone acetyltransferase HBO1 (Histone acetyltransferase binding to origin recognition complex 1, Myst2/Kat7) participates in a range of life processes including DNA replication and tumorigenesis. Recent studies revealed that HBO1 is involved in gene transcriptional activation. However, the molecular behavior of HBO1 in inflammation is yet to be studied. Here we report that endotoxin lipopolysaccharide (LPS) elevates HBO1 protein level via up-regulating UPS25 (ubiquitin specific peptidase 25) and alters inflammatory gene transcription in THP-1 monocytes and in human primary macrophages. LPS protects HBO1 from ubiquitin proteasomal degradation without significantly altering its transcription. By immunoprecipitation, we identified that HBO1 associates with a deubiquitinating enzyme USP25 in THP-1 cells. LPS increases protein level of USP25 resulting in accumulation of HBO1 by suppression of HBO1 ubiquitination. Stabilized-HBO1 modulates inflammatory gene transcription in THP-1 cells. These findings indicate that USP25 promotes stability of HBO1 in bacterial infection thereby enhances HBO1-mediated inflammatory gene transcription.