Fiber-Like Organization as a Basic Principle for Euchromatin Higher-Order Structure

Zakirov, Amir N.; Sosnovskaya, Sophie; Ryumina, Ekaterina D.; Kharybina, Ekaterina; Strelkova, Olga; Zhironkina, Oxana A.; Golyshev, Sergey A.; Moiseenko, Andrey; Kireev, Igor I.

doi:10.3389/fcell.2021.784440

Cited by 8 publications

(5 citation statements)

References 59 publications

(80 reference statements)

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“…Still, it is not clear, how chromatin nanostructures form higher levels of chromatin organization. Employing electron tomography, Zakirov et al 54 demonstrated a fiber-like higher-order structure of about 200 nm in diameter (chromonema) of EdU-labeled chromatin (2 h) detected with biotin-streptavidin-mediated nanogold.…”

Section: Discussionmentioning

confidence: 99%

“…Still, it is not clear, how chromatin nanostructures form higher levels of chromatin organization (Beagrie et al, 2021; Eltsov et al, 2008; Jerkovic and Cavalli, 2021; Minnoye et al, 2021; Zakirov et al, 2022). For an in-depth understanding of these relationships, it is mandatory to produce fully integrated, high-resolution maps, based on the full range of microscopic/biophysical and biochemical approaches (Figure 6c).…”

Section: Discussionmentioning

confidence: 99%

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True-to-scale DNA-density maps correlate with major accessibility differences between active and inactive chromatin

Gelléri

Chen

Szczurek

et al. 2022

Preprint

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Chromatin compaction differences may have a strong impact on accessibility of individual macromolecules and macromolecular assemblies to their DNA target sites. Estimates based on fluorescence microscopy with conventional resolution, however, suggested only modest compaction differences (~2-10x) between active and inactive nuclear compartments (ANC and INC). Here, we present maps of nuclear landscapes with true-to-scale DNA-densities, ranging from <5 Mbp/μm3 to >300 Mbp/μm3. Maps were generated from individual human and mouse cell nuclei with single-molecule localization microscopy at ~20 nm lateral and ~100 nm axial resolution and supplemented by electron spectroscopic imaging. Live cell microinjection experiments with 20 nm and 40 nm sized fluorescent beads, corresponding to macromolecular assemblies for transcription and replication, indicated movements within the ANC, but exclusion from the INC. In line with previous studies of transcription, pulse-chase labeling experiments of DNA demonstrated replication within the ANC, followed by re-location of replicated, inactive chromatin into the INC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

True-to-scale DNA-density maps correlate with major accessibility differences between active and inactive chromatin

Gelléri

Chen

Szczurek

et al. 2022

Preprint

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“…Recent advances in microscopy have enabled the characterization of euchromatin architecture in vivo, revealing disordered chains of nucleosomes with sporadic clusters ( 28 , 30 , 64 , 65 ). The heterogeneous arrangement of euchromatin differs from the conventional 30-nm chromatin fiber model, which was based on in vitro observations ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

“…However, recent studies suggest that in vivo chromatin may exhibit a more heterogeneous architecture ( 28 – 30 ). Euchromatin appears to adopt an open configuration, characterized by disordered nucleosomes separated by variable lengths of linker DNA ( 29 , 30 ).…”

mentioning

confidence: 99%

Physical modeling of nucleosome clustering in euchromatin resulting from interactions between epigenetic reader proteins

Wakim,

Spakowitz

2024

Proc. Natl. Acad. Sci. U.S.A.

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Euchromatin is an accessible phase of genetic material containing genes that encode proteins with increased expression levels. The structure of euchromatin in vitro has been described as a 30-nm fiber formed from ordered nucleosome arrays. However, recent advances in microscopy have revealed an in vivo euchromatin architecture that is much more disordered, characterized by variable-length linker DNA and sporadic nucleosome clusters. In this work, we develop a theoretical model to elucidate factors contributing to the disordered in vivo architecture of euchromatin. We begin by developing a 1D model of nucleosome positioning that captures the interactions between bound epigenetic reader proteins to predict the distribution of DNA linker lengths between adjacent nucleosomes. We then use the predicted linker lengths to construct 3D chromatin configurations consistent with the physical properties of DNA within the nucleosome array, and we evaluate the distribution of nucleosome cluster sizes in those configurations. Our model reproduces experimental cluster-size distributions, which are dramatically influenced by the local pattern of epigenetic marks and the concentration of reader proteins. Based on our model, we attribute the disordered arrangement of euchromatin to the heterogeneous binding of reader proteins and subsequent short-range interactions between bound reader proteins on adjacent nucleosomes. By replicating experimental results with our physics-based model, we propose a mechanism for euchromatin organization in the nucleus that impacts gene regulation and the maintenance of epigenetic marks.

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“…The unit for the resulting metric is arbitrary. Different pairs of parameters are known to lead to similar density maps (Zakirov et al, 2021) . .…”

Section: Ca Segmentation From High Resolution Phase Contrast Microtom...mentioning

confidence: 99%

Distribution of corpora amylacea in the human midbrain: using synchrotron radiation phase-contrast microtomography, high-field magnetic resonance imaging, and histology

Lee,

Mack,

Mattheus

et al. 2023

Front. Neurosci.

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Corpora amylacea (CA) are polyglucosan aggregated granules that accumulate in the human body throughout aging. In the cerebrum, CA have been found in proximity to ventricular walls, pial surfaces, and blood vessels. However, studies showing their three-dimensional spatial distribution are sparse. In this study, volumetric images of four human brain stems were obtained with MRI and phase-contrast X-ray microtomography, followed up by Periodic acid Schiff stain for validation. CA appeared as hyperintense spheroid structures with diameters up to 30 μm. An automatic pipeline was developed to segment the CA, and the spatial distribution of over 200,000 individual corpora amylacea could be investigated. A threefold—or higher—density of CA was detected in the dorsomedial column of the periaqueductal gray (860–4,200 CA count/mm3) than in the superior colliculus (150–340 CA count/mm3). We estimated that about 2% of the CA were located in the immediate vicinity of the vessels or in the peri-vascular space. While CA in the ependymal lining of the cerebral aqueduct was rare, the sub-pial tissue of the anterior and posterior midbrain contained several CA. In the sample with the highest CA density, quantitative maps obtained with MRI revealed high R2* values and a diamagnetic shift in a region which spatially coincided with the CA dense region.

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Fiber-Like Organization as a Basic Principle for Euchromatin Higher-Order Structure

Cited by 8 publications

References 59 publications

True-to-scale DNA-density maps correlate with major accessibility differences between active and inactive chromatin

True-to-scale DNA-density maps correlate with major accessibility differences between active and inactive chromatin

Physical modeling of nucleosome clustering in euchromatin resulting from interactions between epigenetic reader proteins

Distribution of corpora amylacea in the human midbrain: using synchrotron radiation phase-contrast microtomography, high-field magnetic resonance imaging, and histology

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