Author/Authors :
Wang، نويسنده , , Kankan and Wang، نويسنده , , Ping-Ping Shi، نويسنده , , Jiantao and Zhu، نويسنده , , Xuehua and He، نويسنده , , Miaomiao and Jia، نويسنده , , Xiaohong and Yang، نويسنده , , Xianwen and Qiu، نويسنده , , Fei-Fei Jin، نويسنده , , Wen-Han Qian، نويسنده , , Maoxiang and Fang، نويسنده , , Hai and Mi، نويسنده , , Jianqing and Yang، نويسنده , , Xuzhi and Xiao، نويسنده , , Huasheng and Minden، نويسنده , , Mark and Du، نويسنده , , Yanzhi and Chen، نويسنده , , Zhu and Zhang، نويسنده , , Ji، نويسنده ,
Abstract :
Summary
Rα is of crucial importance in acute promyelocytic leukemia (APL) both pathologically and therapeutically. Using a genome-wide approach, we identified in vivo PML/RARα binding sites in a PML/RARα-inducible cell model. Of the 2979 targeted regions, >62% contained canonical PU.1 motifs and >84% of these PU.1 motifs coexisted with one or more RARE half (RAREh) sites in nearby regions. Promoters with such PU.1-RAREh binding sites were transactivated by PU.1. PU.1-mediated transactivation was repressed by PML/RARα and restored by the addition of all-trans retinoic acid (ATRA). Genes containing such promoters were significantly represented by genes transcriptionally suppressed in APL and/or reactivated upon treatment with ATRA. Thus, selective targeting of PU.1-regulated genes by PML/RARα is a critical mechanism for the pathogenesis of APL.
