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Johnathan Whetstine

The Effect of Histone Demethylases on Gene Expression and Cancer Cell Stability (Johnathan Whetstine)

Episode 132

August 29, 2024

In this episode of the Epigenetics Podcast, we talked with Johnathan Whetstine from Fox Chase Cancer Center about his work on the effect of histone demethylases on gene expression and cancer cell stability.

The interview starts by discussing a pivotal paper from Jonathan's lab in 2010, where they identified a role for the KDM4A histone demethylase in replication timing and cell cycle progression. Dr. Whetstine elaborates on the discoveries made regarding the link between histone marks, replication timing, and gene expression control and explains the impact of microRNAs on regulating KDM4A and how protein turnover rates can influence cellular responses to treatments like mTOR inhibitors.

Further, the lab has explored the causal relationship between histone marks and replication timing, demonstrating how alterations in epigenetic regulation can affect genome stability. Jonathan shares insights from his latest research on H3K9 methylation balance at the MLL-KM2A locus, elucidating how these epigenetic modifications regulate amplifications and rearrangements in cancer cells. The episode concludes with a discussion on the establishment of the Cancer Epigenetics Institute at Fox Chase Cancer Center, aiming to bridge academia and industry to accelerate translational research in cancer epigenetics.

 

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References

  • Black, J. C., Allen, A., Van Rechem, C., Forbes, E., Longworth, M., Tschöp, K., Rinehart, C., Quiton, J., Walsh, R., Smallwood, A., Dyson, N. J., & Whetstine, J. R. (2010). Conserved antagonism between JMJD2A/KDM4A and HP1γ during cell cycle progression. Molecular cell, 40(5), 736–748. https://doi.org/10.1016/j.molcel.2010.11.008
  • Mishra, S., Van Rechem, C., Pal, S., Clarke, T. L., Chakraborty, D., Mahan, S. D., Black, J. C., Murphy, S. E., Lawrence, M. S., Daniels, D. L., & Whetstine, J. R. (2018). Cross-talk between Lysine-Modifying Enzymes Controls Site-Specific DNA Amplifications. Cell, 174(4), 803–817.e16. https://doi.org/10.1016/j.cell.2018.06.018
  • Van Rechem, C., Ji, F., Chakraborty, D., Black, J. C., Sadreyev, R. I., & Whetstine, J. R. (2021). Collective regulation of chromatin modifications predicts replication timing during cell cycle. Cell reports, 37(1), 109799. https://doi.org/10.1016/j.celrep.2021.109799
  • Gray, Z. H., Chakraborty, D., Duttweiler, R. R., Alekbaeva, G. D., Murphy, S. E., Chetal, K., Ji, F., Ferman, B. I., Honer, M. A., Wang, Z., Myers, C., Sun, R., Kaniskan, H. Ü., Toma, M. M., Bondarenko, E. A., Santoro, J. N., Miranda, C., Dillingham, M. E., Tang, R., Gozani, O., … Whetstine, J. R. (2023). Epigenetic balance ensures mechanistic control of MLL amplification and rearrangement. Cell, 186(21), 4528–4545.e18. https://doi.org/10.1016/j.cell.2023.09.009

 

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