MacroH2A Function in Development and Disease (Emily Bernstein)

In this episode of the Epigenetics Podcast, we caught up with Emily Bernstein from Icahn Schoon of Medicine at Mount Sinai to talk about her work on MacroH2A function and the role of Polycomb proteins in its epigenetic regulation, and how this affects in stem cell development and disease.

The Bernstein Lab focuses on histone variants, in particular the H2A variant macroH2A. Chromatin architecture is influenced by the composition of the nucleosome and, hence, exchanging the core histones for histone variants can have a major impact on chromatin structure. MacroH2A variantsare the most unique histone variants due to a 30kDa non-histone domain (macro domain) at their C-termini. This macro domain likely confers important functions to macroH2A variants, which have important regulatory roles in the cell. Among other things, the Bernstein Lab has shown that macroH2A is enriched at a critical set of Utx target genes whose expression is critical for the early stages of induced pluripotency, and that macroH2A plays a role as a barrier to tumorigenesis.

References

• Kapoor, A., Goldberg, M. S., Cumberland, L. K., Ratnakumar, K., Segura, M. F., Emanuel, P. O., Menendez, S., Vardabasso, C., LeRoy, G., Vidal, C. I., Polsky, D., Osman, I., Garcia, B. A., Hernando, E., & Bernstein, E. (2010). The histone variant macroH2A suppresses melanoma progression through regulation of CDK8. Nature, 468(7327), 1105–1109. https://doi.org/10.1038/nature09590

• Vardabasso, C., Gaspar-Maia, A., Hasson, D., Pünzeler, S., Valle-Garcia, D., Straub, T., Keilhauer, E. C., Strub, T., Dong, J., Panda, T., Chung, C.-Y., Yao, J. L., Singh, R., Segura, M. F., Fontanals-Cirera, B., Verma, A., Mann, M., Hernando, E., Hake, S. B., & Bernstein, E. (2015). Histone Variant H2A.Z.2 Mediates Proliferation and Drug Sensitivity of Malignant Melanoma. Molecular Cell, 59(1), 75–88. https://doi.org/10.1016/j.molcel.2015.05.009

• Sun, Zhen, Dan Filipescu, Joshua Andrade, Alexandre Gaspar-Maia, Beatrix Ueberheide, and Emily Bernstein. 2018. “Transcription-Associated Histone Pruning Demarcates MacroH2A Chromatin Domains.” Nature Structural & Molecular Biology 25(10):958–70. doi: 10.1038/s41594-018-0134-5.

Related Episodes

• Influence of Histone Variants on Chromatin Structure and Metabolism (Marcus Buschbeck)

• Regulation of Chromatin Organization by Histone Chaperones (Geneviève Almouzni)

• Variants of Core Histones: Modulators of Chromatin Structure and Function (Sandra Hake)

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