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Updated: Jun 12, 2026

A Multilabel Single Molecule Localization Microscopy Protocol for Investigation of Chromatin in the Dense Nuclear Environment
Published on: June 5, 2026
Monte Carlo Simulations indicate that Chromati: Nanostructure is accessible by Light Microscopy
Philipp M Diesinger1, Dieter W Heermann
1Institut für Theoretische Physik Universität Heidelberg Philosophenweg 19 D-69120 Heidelberg Germany. pmdies@mit.edu.
Abstract:
A long controversy exists about the structure of chromatin. Theoretically, this structure could be resolved by scattering experiments if one determines the scattering function - or equivalently the pair distribution function - of the nucleosomes. Unfortunately, scattering experiments with live cells are very difficult and limited to only a couple of nucleosomes.Nevertheless, new techniques like the high-resolution light microscopy supply a new approach to this problem. In this work we determine the radial pair distribution function of chromatin described by our E2A model and find that the dominant peaks which characterize the chromatin structure are very robust in several ways: They can still be identified in the case of chromatin fibers with reasonable linker histone and nucleosome defect rates as well as in the 2D case after a projection like in most high-res light microscopy experiments. This might initiate new experimental approaches like optical microscopy to finally determine the nanostructure of chromatin.Furthermore, we examine the statistics of random chromatin collisions and compare it with 5C data of a gene desert. We find that only chromatin fibers with histone depletion show a significant amount of contacts on the kbp-scale which play a important role in gene regulation. Therefore, linker histone and nucleosome depletion might not only be chromatin defects but even be necessary to facilitate transcription.PACS codes: 82.35.Pq, 87.16.A-, 87.16.af.
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