The role of the DNMT1/UHRF1/USP7 complex in hepatoblastoma

Introduction: The cause for epigenetic alterations found in hepatoblastoma (HB) is still unknown. Recently, we identified a trimeric complex consisting of UHRF1 (ubiquitin-like with PHD and ring finger domains 1), DNMT1 (DNA methyltransferase 1), and USP7 (ubiquitin specific peptidase 7) that stimulates both maintenance and de novo DNA methylation. Methods: Knockdown was done by RNA interference, expression measured by real-time PCR and Western blot, methylation analysis by bisulfite sequencing, and DNA binding by ChIP. Results: UHRF1 binds in concert with DNMT1 and USP7 to promoter regions of tumor suppressor g…