CDDO augments ATRA-induced reactivation of RARβ2 in APL via histone acetylation. Combination of all-trans RA (ATRA) and 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) increases H3-Lys9 acetylation in RARβP2 and RARβ2 transcription. CDDO-bound PPARγ may recruit coactivator proteins, including CBP-p300 and SRC-1 to PPARγ/RXR, which in turn induce histone acetylation and reactivation of ATRA target genes. Ac: acetylated histone H3-Lys9, HDAC: histone deacetylase, mSin3: mammalian homolog of the S. cerevisiae corepressor, Sin 3, NCoR: nuclear receptor corepressor, SRC-1: steroid receptor coactivator-1, CBP/p300: CCAAT/enhancer-binding protein, PCAF: P300/CBP-associated factor.
