Supplementary Materials

Supplementary Material for:

Targeted inhibition of histone H3K27 demethylation is effective in high-risk neuroblastoma

Timothy L. Lochmann, Krista M. Powell, Jungoh Ham, Konstantinos V. Floros, Daniel A. R. Heisey, Richard I. J. Kurupi, Marissa L. Calbert, Maninderjit S. Ghotra, Patricia Greninger, Mikhail Dozmorov, Madhu Gowda, Andrew J. Souers, C. Patrick Reynolds, Cyril H. Benes,* Anthony C. Faber*

*Corresponding author. Email: acfaber{at}vcu.edu (A.C.F.); cbenes{at}mgh.harvard.edu (C.H.B.)

Published 16 May 2018, Sci. Transl. Med. 10, eaao4680 (2018)
DOI: 10.1126/scitranslmed.aao4680

This PDF file includes:

  • Fig. S1. Sensitivity to GSK-J4 is independent of MYCN amplification or p53 functionality.
  • Fig. S2. Sensitivity to GSK-J4 is independent of H3K27 methyltransferase or demethylase expression.
  • Fig. S3. Neuroblastoma cell lines show similar sensitivity to structurally distinct demethylase inhibitors, and JMJD3 is necessary for GSK-J4 sensitivity.
  • Fig. S4. GSK-J4 induces H3K27me3 accumulation in tumors and is well tolerated.
  • Fig. S5. GSK-J4 increases H3K27 methylation in neuroblastoma cell lines.
  • Fig. S6. Multiple differentially expressed genes overlap between cell lines treated with GSK-J4.
  • Fig. S7. GSK-J4 increases differentiation and ER stress markers in the CHLA20 cell line.
  • Fig. S8. GSK-J4 induces apoptosis and cell death.
  • Fig. S9. GSK-J4 induces caspase-3 activity.
  • Fig. S10. Inhibition of caspase cleavage protects against GSK-J4–mediated apoptosis.
  • Fig. S11. BBC3 and ER stress silencing protects from GSK-J4–induced cell death.
  • Fig. S12. Statistical analysis shows gene expression overlap between GSK-J4 and RA treatment of neuroblastoma cell lines.
  • Fig. S13. GSK-J4 induces axonal outgrowth in LAN5 cells.
  • Fig. S14. GSK-J4 synergizes with RA in GSK-J4– and RA-resistant cell lines.
  • Fig. S15. GSK-J4 combines with venetoclax.
  • Fig. S16. Combination of GSK-J4 and venetoclax is tolerated in xenograft models.

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Other Supplementary Material for this manuscript includes the following:

  • Table S1 (Microsoft Excel format). Cell line information and GSK-J4 screen data.
  • Table S2 (Microsoft Excel format). Genetic information for neuroblastoma cell lines from GSK-J4 screen.
  • Table S3 (Microsoft Excel format). Significant differentially expressed genes from GSK-J4 RNA-seq.
  • Table S4 (Microsoft Excel format). Differentially expressed gene overlaps in cell lines from GSK-J4 RNA-seq.
  • Table S5 (Microsoft Excel format). Functional pathways from IPA analysis.
  • Table S6 (Microsoft Excel format). Genes reported from neuritogenesis IPA pathway.
  • Table S7 (Microsoft Excel format). Gene names from Fisher’s exact test and GSEA comparisons.
  • Table S8 (Microsoft Excel format). Common affected genes between GSK-J4 and EPZ-6438 treatment in the IMR5 cell line.
  • Table S9 (Microsoft Excel format). Primary data.

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