In this episode of the Epigenetics Podcast, we talked with Eva Nogales from UC Berkeley about her work on Cryo-EM and the Dynamics of TFIID and PRC2.

We explore the origins of Dr. Nogales's fascination with biology and how her academic journey shifted from physics into the realms of biophysics and structural biology. She shares the profound impact of her training under physicists who instilled a rigorous, quantitative approach to problem-solving, a perspective that continues to influence her work. The importance of visualization emerges as a central theme, showcasing how critical imagery can foster understanding even amidst complex biological structures.

A particular focus of our discussion centers on the transcription factor complex TFIID, a significant milestone in Dr. Nogales's career. She recalls the challenging journey to uncovering its structure for the first time, which involved navigating numerous technical hurdles. Dr. Nogales details how their innovative approaches led to insights about the conformational flexibility and functional dynamics of TFIID, especially in relation to its interactions with DNA during transcription initiation. The richness of this narrative reflects both the perseverance required in scientific discovery and the serendipity that often accompanies groundbreaking breakthroughs.

Transitioning into the epigenetics realm, Dr. Nogales elucidates the critical role of PRC2 in gene silencing and cellular identity preservation. With a focus on chromatin and nucleosome interactions, we unpack the intricate mechanisms by which PRC2 functions in the context of chromatin remodeling and gene regulation. Dr. Nogales recounts how collaborations and the imaginative contributions of her lab members led to novel research trajectories, particularly the elucidation of structural states of PRC2 bound to chromatin and characterized by novel methodologies developed within her lab.

Further, our discussion touches on Dr. Nogales’s recent findings regarding the nuanced interplay of various cofactors involved in PRC2's regulatory functions. We delve into her exciting projects aiming to bring further clarity to the complex dynamics of chromatin interaction and the distinct forms of PRC2. Dr. Nogales's unyielding commitment to research is mirrored in her ambition to explore unresolved questions surrounding these multifaceted biological processes.

References

Andel F 3rd, Ladurner AG, Inouye C, Tjian R, Nogales E. Three-dimensional structure of the human TFIID-IIA-IIB complex. Science. 1999 Dec 10;286(5447):2153-6. doi: 10.1126/science.286.5447.2153. PMID: 10591646.
Cianfrocco MA, Kassavetis GA, Grob P, Fang J, Juven-Gershon T, Kadonaga JT, Nogales E. Human TFIID binds to core promoter DNA in a reorganized structural state. Cell. 2013 Jan 17;152(1-2):120-31. doi: 10.1016/j.cell.2012.12.005. PMID: 23332750; PMCID: PMC3552382.
Yang Z, Mameri A, Cattoglio C, Lachance C, Florez Ariza AJ, Luo J, Humbert J, Sudarshan D, Banerjea A, Galloy M, Fradet-Turcotte A, Lambert JP, Ranish JA, Côté J, Nogales E. Structural insights into the human NuA4/TIP60 acetyltransferase and chromatin remodeling complex. Science. 2024 Aug 23;385(6711):eadl5816. doi: 10.1126/science.adl5816. Epub 2024 Aug 23. PMID: 39088653.

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Cryo-EM and the Dynamics of TFIID and PRC2 (Eva Nogales)