Bmi1 cooperates with Dnmt1-associated protein 1 in gene silencing

Polycomb group (PcG) proteins are involved in gene silencing through chromatin modifications. Among polycomb repressive complexes (PRCs), PRC1 exhibits H2A-KI 19 ubiquitin E3 ligase activity. However, the molecular mechanisms underlying PRC1-mediated gene silencing remain largely obscure. In this study, we found that Bmi1 directly interacts with Drant-associated protein 1 (Dmapl), which has been characterized to associate with the maintenance DNA methyltransferase, Dnmt1. Bmil was demonstrated to form a ternary complex with Dmapl and Dnmtl with Dmapl in the central position. Chromatin immunoprecipitations confirmed the ternary complex formation within the context of the PRC1 at the Bmil target loci. Loss of Dmapl binding to the Bmil target loci was tightly associated with derepressed gene expression in Bmil(-/-) cells. Dmap1 knockdown exhibited the same impact as Bmil knockout did on the expression of Bmil targets, including Hox genes. Collectively, our findings suggest that Bmil incorporates Dmap1 in polycomb gene silencing. (c) 2006 Elsevier Inc. All rights reserved.