Deciphering Chromatin Architecture in Super-Resolution with Dr. Neguembor

The three-dimensional folding of genes within the nuclear space is integral to understanding gene function and regulation, moving beyond the linear DNA sequence. Dr. Neguembor presents immuno-OligoSTORM, a revolutionary imaging strategy that super-resolves the distribution of nucleosomes within specific genes by simultaneously visualizing DNA and histones. In this episode, we dive into the technology behind immuno-OligoSTORM and how it integrates with restraint-based and coarse-grained modeling approaches to sync super-resolution imaging data with Hi-C contact frequencies and deconvoluted micrococcal nuclease-sequencing information. This results in Modeling immuno-OligoSTORM, a method that allows for quantitative modeling of genes with nucleosome resolution and reveals information about chromatin accessibility for regulatory factors, like RNA polymerase II.Join us as Dr. Neguembor elucidates how Modeling immuno-OligoSTORM allows exploration of intercellular variability, transcriptional-dependent gene conformation, and the folding of housekeeping and pluripotency-related genes in human pluripotent and differentiated cells. This conversation promises to provide the highest degree of data integration on this subject so far.Key Words: immuno-OligoSTORM, Super-Resolution Imaging, Chromatin Architecture, DNA Folding, Nucleosomes, Restraint-based Modeling, Coarse-Grained Modeling, Hi-C Contact Frequencies, Micrococcal Nuclease-Sequencing, RNA Polymerase II.Neguembor, et al. MiOS, an integrated imaging and computational strategy to model gene folding with nucleosome resolution. Nat Struct Mol Biol 29, (2022). https://doi.org/10.1038/s41594-00839-y