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.
Original language | English |
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Pages (from-to) | 186-97 |
Number of pages | 12 |
Journal | Cancer Cell |
Volume | 17 |
Issue number | 2 |
DOIs | |
Publication status | Published - 17 Feb 2010 |
Bibliographical note
2010 Elsevier Inc. All rights reserved.Keywords
- Humans
- Gene Expression Regulation, Leukemic
- Binding Sites
- Base Sequence
- Promoter Regions, Genetic
- Proto-Oncogene Proteins
- Chromatin Immunoprecipitation
- Leukemia, Promyelocytic, Acute
- Molecular Sequence Data
- Myeloid Cells
- Consensus Sequence
- Trans-Activators
- Cell Line
- Oncogene Proteins, Fusion