PML/RARα Targets Promoter Regions Containing PU.1 Consensus and RARE Half Sites in Acute Promyelocytic Leukemia

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• 作者：Kankan Wang ; Ping Wang ; Jiantao Shi ; Xuehua Zhu ; Miaomiao He ; Xiaohong Jia ; Xianwen Yang ; Fei Qiu ; Wen Jin ; Maoxiang Qian ; Hai Fang ; Jianqing Mi ; Xuzhi Yang ; Huasheng Xiao ; Mark Minden ; Yanzhi Du ; Zhu
• 刊名：Cancer Cell
• 出版年：2010
• 出版时间：17 February 2010
• 年：2010
• 卷：17
• 期：2
• 页码：186-197
• 全文大小：1431 K

文摘

Summary

PML/RARα 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.