Table 1.
Miniscreen for Epigenetic Regulators of FXN Silencing During Reprogramming
| Compound (abbreviation) | Target | Process | Concentration |
|---|---|---|---|
| HDAC inhibitor 4b (4b)a | HDAC3 | Histone acetylation | 5 μM |
| Sodium butyrate (NaB) | HDAC class I | Histone acetylation | 0.5 mM |
| Tranylcypromine, Parnate (Par) | LSD1 | Histone H3K4 methylation | 4 μM |
| Tubastatin A (TubA) | HDAC6 | Histone acetylation | 5 μM |
| RG108 (RG) | DNMT | CpG methylation | 5 μM |
| BIX01294 (BIX) | G9a | Histone H3K9 methylation | 4 μM |
| Epi-ML (EML)b | Multiple | Multiple targets | 5 μM |
| DMSO | Control | — | — |
Only compounds that resulted in successful establishment of iPSC clones are shown.
a
HDACi 4b has been demonstrated to increase expression of the FXN gene in FRDA lymphoid cells and neurons, but not in FRDA fibroblasts or iPSCs.
b
Epigenetic Multiple Ligand (Epi-ML; Calbiochem) is a cell-permeable bis-arylidene compound that inhibits several mammalian histone-modifying enzymes, including SET7, PRMT1, p300/CBP, and SIRT1/2.
DMSO, dimethyl sulfoxide; EML, Epigenetic Multiple Ligand; FRDA, Friedreich's ataxia; FXN, frataxin; HDACi, histone deacetylase inhibitors; iPSCs, induced pluripotent stem cells.