| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2107701 | Cancer Cell | 2010 | 12 Pages |
SummaryPML/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.
Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (151 K)Download as PowerPoint slideHighlights► PML/RARα is recruited to PU.1-bound chromatin containing RARE half and PU.1 sites ► PML/RARα is capable of suppressing PU.1-mediated transactivation ► Repression of PU.1-mediated transcription by PML/RARα can be relieved by ATRA ► Selective targeting of PU.1-regulated genes by PML/RARα is essential in APL
