In this episode of the Epigenetics Podcast, we talked with Sven Heinz from the University of California in San Diego about his work on the impact of sequence variation on transcription factor binding affinities and genetic diversity.

Sven Heinz talks about a landmark study published in Nature that examined the impact of sequence variation on transcription factor binding affinities and downstream effects on gene expression. Modifying genetic sequences to understand the influence of different motifs provided valuable insights into how genetic variation shapes cellular responses and gene expression patterns, underscoring the importance of genetic diversity.

Methodological approaches using inducible systems to observe changes in transcription factor binding patterns highlight the critical role of motif variation and redundancy in transcription factor families. These studies provide essential insights into the complex network of transcriptional regulation and chromatin dynamics, revealing the nuanced mechanisms that control gene expression and chromatin organization. In addition, he is investigating how small nucleotide changes can significantly affect transcription factor binding in macrophages from different mouse strains, shedding light on the intricate effects of genetic variation on transcription factor binding.

Sven's career path from project scientist to assistant professor at UC San Diego and the Salk Institute reflects a journey marked by serendipitous opportunities and a collaborative, innovative research environment. The podcast delves into the effects of influenza virus infection on chromosomal territories, gene transcription, and chromatin structure, unraveling the sophisticated interplay between viral infection and host cell transcriptional regulation.

Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y. C., Laslo, P., Cheng, J. X., Murre, C., Singh, H., & Glass, C. K. (2010). Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Molecular cell, 38(4), 576–589. https://doi.org/10.1016/j.molcel.2010.05.004

Heinz, S., Romanoski, C. E., Benner, C., Allison, K. A., Kaikkonen, M. U., Orozco, L. D., & Glass, C. K. (2013). Effect of natural genetic variation on enhancer selection and function. Nature, 503(7477), 487–492. https://doi.org/10.1038/nature12615

Texari, L., Spann, N. J., Troutman, T. D., Sakai, M., Seidman, J. S., & Heinz, S. (2021). An optimized protocol for rapid, sensitive and robust on-bead ChIP-seq from primary cells. STAR protocols, 2(1), 100358. https://doi.org/10.1016/j.xpro.2021.100358

Pioneer Transcription Factors and Their Influence on Chromatin Structure (Ken Zaret)

Multiple Challenges in ChIP (Adam Blattler)

The Role of Pioneer Factors Zelda and Grainyhead at the Maternal-to-Zygotic Transition (Melissa Harrison)

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