In this episode of the Epigenetics Podcast, we talked with Patrick Murphy from Cornell University about his work on gene regulation and cellular identity.

Dr. Murphy's research focuses on the molecular mechanisms that govern gene expression through transcriptional and chromatin-based regulatory networks. At the start of the Interview Dr. Murphy describes an innovative single-molecule analytical approach he developed during his early research. This method enables the simultaneous detection of multiple epigenetic marks and contributes to his foundational studies on chromatin biology. Focusing on chromatin states, he introduces the concept of placeholder nucleosomes which are specialised nucleosomes that play key roles in maintaining a permissive chromatin state and facilitating gene activation during embryonic development.

The discussion further explores Dr. Murphy's transition from studying Drosophila to working with zebrafish, highlighting his focus on chromatin reprogramming during zygotic genome activation. He presents data from his collaborations that reveal intriguing roles for specific chromatin marks, emphasising how these discoveries hold potential for understanding gene expression regulation in both zebrafish and mammalian models.

Dr. Murphy also shares insights into a project investigating the impacts of paternal cigarette smoke on offspring health, which led to an exploration of systemic inflammation responses and their lasting effects on gene expression in the brain. This unique intersection of basic and translational research underlines the wide-ranging implications of his findings.

• Murphy, P. J., Cipriany, B. R., Wallin, C. B., Ju, C. Y., Szeto, K., Hagarman, J. A., Benitez, J. J., Craighead, H. G., & Soloway, P. D. (2013). Single-molecule analysis of combinatorial epigenomic states in normal and tumor cells. Proceedings of the National Academy of Sciences of the United States of America, 110(19), 7772–7777. https://doi.org/10.1073/pnas.1218495110
• Murphy, P. J., Wu, S. F., James, C. R., Wike, C. L., & Cairns, B. R. (2018). Placeholder Nucleosomes Underlie Germline-to-Embryo DNA Methylation Reprogramming. Cell, 172(5), 993–1006.e13. https://doi.org/10.1016/j.cell.2018.01.022
• Park, B. J., Hua, S., Casler, K. D., Cefaloni, E., Ayers, M. C., Lake, R. F., Murphy, K. E., Vertino, P. M., O'Connell, M. R., & Murphy, P. J. (2025). CUT&Tag overcomes biases of ChIP and establishes chromatin patterns for repetitive genomic loci. iScience, 28(11), 113757. https://doi.org/10.1016/j.isci.2025.113757

• Pioneer Transcription Factors and Their Influence on Chromatin Structure (Ken Zaret)
• In Vivo Nucleosome Structure and Dynamics (Srinivas Ramachandran)
• Nucleosome Positioning in Cancer Diagnostics (Vladimir Teif)

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In this episode of the Epigenetics Podcast, we talked with Srinjan Basu from Imperial College London to talk about his work on how chromatin architecture and epigenetic mechanisms orchestrate developmental gene expression programs.

We begin by exploring Dr. Basu's early work at Harvard which involved pioneering Raman-based label-free imaging, allowing the study of chromatin dynamics in live tissue. Here, he tackles technical challenges faced in visualizing DNA interactions, emphasizing the shift from 2D to 3D analysis and the importance of real-time observation of chromatin behavior under various conditions. This segues into his groundbreaking research on single transcription factors interacting with chromatin, revealing subtle but significant changes in the dynamics of gene regulation.

We transition into the complexities of chromatin architecture as Dr. Basu recounts his efforts in mapping the entire mouse genome in single pluripotent cells, unearthing unexpected heterogeneity among cells. This heterogeneity raises intriguing questions about its impact on cellular function, prompting ongoing investigations into chromatin dynamics and the role of remodeling complexes like NuRD in cell fate transitions.

Dr. Basu elucidates how recent studies have begun to bridge the gaps in understanding how transcription factors and chromatin dynamics interact during cellular decisions, particularly emphasizing the influence of mechanical signals and the intrinsic properties of cells. His research underscores the idea that stem cells undergo a preparatory phase for differentiation, highlighting the critical balance of intrinsic and extrinsic factors that govern genetic expression and cellular outcomes.

We also talk about Dr. Basu's current research trajectory, focusing on enhancing imaging techniques to study gene dynamics in tissue contexts relevant to developmental biology and disease states. He illustrates a vision for future projects that integrate advanced imaging tools to investigate transcription factor dynamics and chromatin interactions in live cells and embryos, furthering the understanding of decision-making processes in cellular contexts.

• Stevens TJ, Lando D, Basu S, et al. 3D structures of individual mammalian genomes studied by single-cell Hi-C. Nature. 2017 Apr;544(7648):59-64. DOI: 10.1038/nature21429. PMID: 28289288; PMCID: PMC5385134.

• Basu S, Needham LM, Lando D, et al. FRET-enhanced photostability allows improved single-molecule tracking of proteins and protein complexes in live mammalian cells. Nature Communications. 2018 Jun;9(1):2520. DOI: 10.1038/s41467-018-04486-0. PMID: 29955052; PMCID: PMC6023872.

• Advanced Optical Imaging in 3D Nuclear Organisation (Lothar Schermelleh)

• Analysis of 3D Chromatin Structure Using Super-Resolution Imaging (Alistair Boettiger)

• Single-Molecule Imaging of the Epigenome (Efrat Shema)

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• Dr. Stefan Dillinger on LinkedIn

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• Email: podcast@activemotif.com