In this episode of the Epigenetics Podcast, we talked with Yali Dou from Keck School of Medicine of USC about her work on MLL Proteins in Mixed-Lineage Leukemia.
To start off this Interview Yali describes her early work on MLL1 and its function in transcription, particularly its involvement in histone modification. She explains her successful purification of the MLL complex and the discovery of MOF as one of the proteins involved.
Next, the interview focuses on her work in reconstituting the MLL core complex and the insights gained from this process. She shares her experience of reconstituting the MLL complex and discusses her focus on the crosstalk of H3K4 and H3K79 methylation, regulated by H2BK34 ubiquitination.
The podcast then delves into the therapeutic potential of MLL1, leading to the discovery of a small molecule inhibitor. Finally, we talk about the importance of the protein WDR5 in the assembly of MLL complexes and how targeting the WDR5-ML interaction can inhibit MLL activity.
References
Dou, Y., Milne, T., Ruthenburg, A. et al. Regulation of MLL1 H3K4 methyltransferase activity by its core components. Nat Struct Mol Biol 13, 713–719 (2006). https://doi.org/10.1038/nsmb1128
Wu, L., Zee, B. M., Wang, Y., Garcia, B. A., & Dou, Y. (2011). The RING Finger Protein MSL2 in the MOF Complex Is an E3 Ubiquitin Ligase for H2B K34 and Is Involved in Crosstalk with H3 K4 and K79 Methylation. Molecular Cell, 43(1), 132–144. https://doi.org/10.1016/j.molcel.2011.05.015
Cao, F., Townsend, E. C., Karatas, H., Xu, J., Li, L., Lee, S., Liu, L., Chen, Y., Ouillette, P., Zhu, J., Hess, J. L., Atadja, P., Lei, M., Qin, Z. S., Malek, S., Wang, S., & Dou, Y. (2014). Targeting MLL1 H3K4 Methyltransferase Activity in Mixed-Lineage Leukemia. Molecular Cell, 53(2), 247–261. https://doi.org/10.1016/j.molcel.2013.12.001
Park, S.H., Ayoub, A., Lee, YT. et al. Cryo-EM structure of the human MLL1 core complex bound to the nucleosome. Nat Commun 10, 5540 (2019). https://doi.org/10.1038/s41467-019-13550-2
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The Role of Non-Histone Proteins in Chromosome Structure and Function During Mitosis (Bill Earnshaw)
Effects of DNA Methylation on Chromatin Structure and Transcription (Dirk Schübeler)
CpG Islands, DNA Methylation, and Disease (Adrian Bird)
Biophysical Modeling of 3-D Genome Organization (Leonid Mirny)
From Nucleosome Structure to Function (Karolin Luger)
Identification of Functional Elements in the Genome (Bing Ren)
Hi-C and Three-Dimensional Genome Sequencing (Erez Lieberman Aiden)
Chromatin Structure and Dynamics at Ribosomal RNA Genes (Tom Moss)
Epigenetic Origins Of Heterogeneity And Disease (Andrew Pospisilik)
PIXUL: On the Leading Edge of Chromatin Shearing (Karol Bomsztyk and Tom Matula)
Influence of Histone Variants on Chromatin Structure and Metabolism (Markus Buschbeck)
Epigenetic Mechanisms of Aging and Longevity (Shelley Berger)
Epigenetics & Glioblastoma: New Approaches to Treat Brain Cancer (Lucy Stead)
The Past, Present, and Future of Epigenetics (Joe Fernandez, founder of Active Motif)
The Interchromatin Network Model (Ana Pombo)
Dosage Compensation in Drosophila (Asifa Akhtar)
Spatial Organization of the Human Genome (Wendy Bickmore)
Heterochromatin and Phase Separation (Gary Karpen)
Diabetes and Epigenetics (Jean-Sébastien Annicotte)
Epigenetics and X-inactivation (Edith Heard)
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