In this episode of the Epigenetics Podcast, we talked with Boyan Bonev from the HelmholtzZetrum in Munich about his work on neuroepigenetics, focusing on gene regulation, chromatin architecture, and primate epigenome evolution,

This Episode focuses on Dr. Bonev’s recent research, particularly focusing on how chromatin architecture and gene regulation influence neural cell identity and function. He discusses his work investigating transcriptional activity in relation to chromatin insulation, highlighting a critical finding that induced expression of genes does not necessarily lead to chromatin insulation—a point that complicates prior assumptions about the relationship between gene expression and chromatin organization. This study aimed to determine the causal versus correlative aspects of chromatin architecture in brain development and links it to developmental processes and neurodevelopmental disorders.

Building on his findings in gene regulation, Dr. Bonev elaborates on a significant study he conducted in his own lab, where he mapped the regulatory landscape of neural differentiation in the mouse neocortex. Here, he employed cutting-edge single-cell sequencing methodologies to analyze intricate gene and enhancer interactions, revealing that selective enhancer-promoter interactions are primarily cell-type specific. This nuanced understanding aids in deciphering the complexities associated with gene expression as it relates to neural stem cells and differentiated neurons, emphasizing the importance of single-cell analyses over bulk sequencing methods.

Moreover, Dr. Bonev reveals a novel methodology developed in his lab that allows for the simultaneous assessment of spatial genome organization, chromatin accessibility, and DNA methylation at high resolution. This advancement not only reduces costs but also enhances the potential to correlate higher-dimensional genomic data with specific biological questions, fostering a more integrative approach to understanding genetic regulation.

The discussion then shifts focus towards Dr. Bonev's recent project profiling primate epigenome evolution, where he investigated the 3D genome organization, chromatin accessibility, and gene expression among iPSCs and neural stem cells from various species, including humans, chimpanzees, gorillas, and macaques. In this research, he identifies trends related to transcription factor evolution and chromatin modifications across species. The insights gleaned from this work underscore the evolutionary significance of structural variations in the 3D genome, pointing to a possible link between chromatin dynamics and the evolutionary development of the primate brain.

Bonev B, Mendelson Cohen N, Szabo Q, Fritsch L, Papadopoulos GL, Lubling Y, Xu X, Lv X, Hugnot JP, Tanay A, Cavalli G. Multiscale 3D Genome Rewiring during Mouse Neural Development. Cell. 2017 Oct 19;171(3):557-572.e24. doi: https://doi.org/10.1016/j.cell.2017.09.043. PMID: 29053968; PMCID: PMC5651218.

Noack, F., Vangelisti, S., Raffl, G. et al. Multimodal profiling of the transcriptional regulatory landscape of the developing mouse cortex identifies Neurog2 as a key epigenome remodeler. Nat Neurosci 25, 154–167 (2022). https://doi.org/10.1038/s41593-021-01002-4

Noack F, Vangelisti S, Ditzer N, Chong F, Albert M, Bonev B. Joint epigenome profiling reveals cell-type-specific gene regulatory programmes in human cortical organoids. Nat Cell Biol. 2023 Dec;25(12):1873-1883. doi: 10.1038/s41556-023-01296-5. Epub 2023 Nov 23. PMID: 37996647; PMCID: PMC10709149.

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Polycomb Proteins, Gene Regulation, and Genome Organization in Drosophila (Giacomo Cavalli)

The Effect of lncRNAs on Chromatin and Gene Regulation (John Rinn)

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