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
Related Episodes
Dosage Compensation in Drosophila (Asifa Akhtar)
Targeting COMPASS to Cure Childhood Leukemia (Ali Shilatifard)
Contact
Epigenetics Podcast on X
Epigenetics Podcast on Instagram
Epigenetics Podcast on Mastodon
Epigenetics Podcast on Bluesky
Epigenetics Podcast on Threads
Active Motif on X
Active Motif on LinkedIn
Email: podcast@activemotif.com
H3K4me3, Set-Proteins, Isw1 and their Role in Transcription (Jane Mellor)
The role of DNA Methylation in Epilepsy (Katja Kobow)
MacroH2A Function in Development and Disease (Emily Bernstein)
Spatio-Temporal Alterations in Chromosome Dynamics (Jane Skok)
Chromatin Organization During Development and Disease (Marieke Oudelaar)
Enhancers and Chromatin Remodeling in Mammary Gland Development (Camila dos Santos)
The Role of SMCHD1 in Development and Disease (Marnie Blewitt)
Single-Molecule Imaging of the Epigenome (Efrat Shema)
Heterochromatin Protein 1 and its Influence on the Structure of Chromatin (Serena Sanulli)
The Effects of Early Life Stress on Mammalian Development (Catherine J. Peña)
Targeting COMPASS to Cure Childhood Leukemia (Ali Shilatifard)
Effects of Non-Enzymatic Covalent Histone Modifications on Chromatin (Yael David)
ATAC-Seq, scATAC-Seq and Chromatin Dynamics in Single-Cells (Jason Buenrostro)
Synthetic Chromatin Epigenetics (Karmella Haynes)
Development of Integrative Machine Learning Tools for Neurodegenerative Diseases (Enrico Glaab)
Ultraconserved Enhancers and Enhancer Redundancy (Diane Dickel)
Variants of Core Histones: Modulators of Chromatin Structure and Function (Sandra Hake)
DNA Methylation and Mammalian Development (Déborah Bourc'his)
Chromatin Analysis using Mass Spectrometry (Axel Imhof)
Chromatin Profiling: From ChIP to CUT&RUN, CUT&Tag and CUTAC (Steven Henikoff)
Create your
podcast in
minutes
It is Free
DNA Today: A Genetics Podcast
Museum of the Missing
Strange by Nature Podcast
Sasquatch Chronicles
Hidden Brain