Bmi1 cooperates with Dnmt1-associated protein 1 in gene silencing.

Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

Biochemical and biophysical research communications 2007 Feb 23

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Polycomb group (PcG) proteins are involved in gene silencing through chromatin modifications. Among polycomb repressive complexes (PRCs), PRC1 exhibits H2A-K119 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 Dnmt-associated protein 1 (Dmap1), which has been characterized to associate with the maintenance DNA methyltransferase, Dnmt1. Bmi1 was demonstrated to form a ternary complex with Dmap1 and Dnmt1 with Dmap1 in the central position. Chromatin immunoprecipitations confirmed the ternary complex formation within the context of the PRC1 at the Bmi1 target loci. Loss of Dmap1 binding to the Bmi1 target loci was tightly associated with derepressed gene expression in Bmi1-/- cells. Dmap1 knockdown exhibited the same impact as Bmi1 knockout did on the expression of Bmi1 targets, including Hox genes. Collectively, our findings suggest that Bmi1 incorporates Dmap1 in polycomb gene silencing.

Citation

Masamitsu Negishi, Atsunori Saraya, Satoru Miyagi, Kenji Nagao, Yoshimasa Inagaki, Mitsuo Nishikawa, Shoji Tajima, Haruhiko Koseki, Hiroshi Tsuda, Yoshinari Takasaki, Hiromitsu Nakauchi, Atsushi Iwama. Bmi1 cooperates with Dnmt1-associated protein 1 in gene silencing. Biochemical and biophysical research communications. 2007 Feb 23;353(4):992-8