BRD7, a novel bromodomain gene, inhibits G1-S progression by transcriptionally regulating some important molecules involved in ras/MEK/ERK and Rb/E2F pathways

Bromodomain is a 110 amino acid domain. It is evolutionally conserved and is found in proteins strongly implicated in signal-dependent transcriptional regulation. BRD7 is a novel bromodomain gene and it is downexpressed in nasopharyngeal carcinoma (NPC) biopsies and cell lines; its function is poorly understood. In the present study, tet-on inducible expression system was used to investigate the role of BRD7 in cell growth and cell cycle progression. We found that ectopic expression of BRD7 in NPC cells inhibited cell growth and cell cycle progression from G1 to S. We further performed cell cycle cDNA array to screen potential transcriptional targets of BRD7 in cell cycle. Thirteen important signaling molecules, mainly implicated in ras/MEK/ERK and Rb/E2F pathways, were differentially expressed by induction of BRD7. Moreover, we observed that BRD7 could regulate the promoter activity of E2F3, one of its targets. Taken together, the present study indicated that BRD7 inhibited G1-S progression by transcriptionally regulating some important molecules involved in ras/MEK/ERK and Rb/E2F pathways and suggested that BRD7 may present a promising candidate of NPC(TM) associated tumor suppressor gene. (C) 2004 Wiley-Liss, Inc.