| Literature DB >> 20159610 |
Kankan Wang1, 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 Chen, Ji Zhang.
Abstract
PML/RARalpha is of crucial importance in acute promyelocytic leukemia (APL) both pathologically and therapeutically. Using a genome-wide approach, we identified in vivo PML/RARalpha binding sites in a PML/RARalpha-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/RARalpha 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/RARalpha is a critical mechanism for the pathogenesis of APL. 2010 Elsevier Inc. All rights reserved.Entities:
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Year: 2010 PMID： 20159610 DOI： 10.1016/j.ccr.2009.12.045
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743