Chromatin Fibers Are Formed by Heterogeneous Groups of Nucleosomes In Vivo

Ricci, Maria Aurelia; Manzo, Carlo; García‐Parajó, María F.; Lakadamyali, Melike; Cosma, María Pía

doi:10.1016/j.cell.2015.01.054

Cited by 585 publications

(713 citation statements)

References 53 publications

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“…These cells divide approximately once per hour (Kimmel et al, 1995), allowing the frequent observation of transcription onset and establishment of chromatin organization after mitosis. Similar to other non-differentiated cells (Ahmed et al, 2010;Ricci et al, 2015), late blastula cells exhibit no permanently compacted heterochromatin (SI Figure 1). This simplifies our analysis by limiting it to euchromatin.…”

Section: Transcription Onset Establishes Microenvironments That Organsupporting

confidence: 57%

“…During the interphase of the cell cycle, when DNA is transcribed into RNA, chromatin exhibits a dynamic, three-dimensional organization (Cremer and Cremer, 2001;Pombo and Branco, 2007;Nagano et al, 2017;Nozaki et al, 2017). Although chromatin organization has often been described in terms of structures with discrete length scales, recent work has suggested that it is characterized by a continuum of packing densities (Ricci et al, 2015;Ou et al, 2017). This raises the question how such packing is achieved.…”

Section: Introductionmentioning

confidence: 99%

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Transcription organizes euchromatin similar to an active microemulsion

Hilbert

Sato

Kimurâ

et al. 2017

Preprint

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Graphical abstract HighlightsThe copyright holder for this preprint (which was . http://dx.doi.org/10.1101/234112 doi: bioRxiv preprint first posted online Dec. 15, 2017; Page 2 of 46 SummaryThe three-dimensional organization of the genome is essential for development and health. Although the organization of euchromatin (transcriptionally permissive chromatin) dynamically adjusts to changes in transcription, the underlying mechanisms remain elusive. Here, we studied how transcription organizes euchromatin, using experiments in zebrafish embryonic cells and theory. We show that transcription establishes an interspersed pattern of chromatin domains and RNA-enriched microenvironments. Specifically, accumulation of RNA in the vicinity of transcription sites creates microenvironments that locally remodel chromatin by displacing not transcribed chromatin. Ongoing transcriptional activity stabilizes the interspersed pattern of chromatin domains and RNA-enriched microenvironments by establishing contacts between chromatin and RNA. We explain our observations with an active microemulsion model based on two macromolecular mechanisms: RNA/RNA-binding protein complexes generally segregate from chromatin, while transcribed chromatin is retained among RNA/RNA-binding protein accumulations. We propose that microenvironments might be central to genome architecture and serve as gene regulatory hubs.

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Section: Transcription Onset Establishes Microenvironments That Organsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Transcription organizes euchromatin similar to an active microemulsion

Hilbert

Sato

Kimurâ

et al. 2017

Preprint

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“…4 B and C shows the corresponding DNA-PLM images at different scales (also see Movie S1 for raw images and the DNA-PLM reconstruction). Clearly, the macromolecular organization of nucleic acid structures is arranged in discrete nanoclusters in interphase nuclei, which is consistent with previous reports (9,41). We further plotted the density image by defining the density as the number of stochastic emission events per pixel (Fig.…”

Section: Resultssupporting

confidence: 88%

“…4G) and the number of emission events per nanocluster (Fig. 4H), which can be useful in understanding the nanoscale organization of chromatin (41).…”

Section: Resultsmentioning

confidence: 99%

Superresolution intrinsic fluorescence imaging of chromatin utilizing native, unmodified nucleic acids for contrast

Dong

Almassalha

Stypula-Cyrus

et al. 2016

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

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Visualizing the nanoscale intracellular structures formed by nucleic acids, such as chromatin, in nonperturbed, structurally and dynamically complex cellular systems, will help expand our understanding of biological processes and open the next frontier for biological discovery. Traditional superresolution techniques to visualize subdiffractional macromolecular structures formed by nucleic acids require exogenous labels that may perturb cell function and change the very molecular processes they intend to study, especially at the extremely high label densities required for superresolution. However, despite tremendous interest and demonstrated need, label-free optical superresolution imaging of nucleotide topology under native nonperturbing conditions has never been possible. Here we investigate a photoswitching process of native nucleotides and present the demonstration of subdiffraction-resolution imaging of cellular structures using intrinsic contrast from unmodified DNA based on the principle of single-molecule photon localization microscopy (PLM). Using DNA-PLM, we achieved nanoscopic imaging of interphase nuclei and mitotic chromosomes, allowing a quantitative analysis of the DNA occupancy level and a subdiffractional analysis of the chromosomal organization. This study may pave a new way for label-free superresolution nanoscopic imaging of macromolecular structures with nucleotide topologies and could contribute to the development of new DNA-based contrast agents for superresolution imaging.superresolution fluorescence microscopy | label-free imaging | nucleic acids | chromatin topology | chromosome A dvances in genomics and molecular biology over the past decades revolutionized our knowledge of biological systems. Despite our expanded understanding of biological interactions, there continues to be a limited understanding of these complex molecular processes in nonperturbed, structurally and dynamically complex cellular systems (1). As such, it is of critical importance to develop methods that allow direct visualization of nanoscale structures where these processes take place in their native states. Recently, superresolution fluorescence microscopy techniques, including stimulated emission depletion microscopy, structured illumination microscopy, and photon localization microscopy (PLM), such as photoactivated localization microscopy and stochastic optical reconstruction microscopy (STORM), have extended the ultimate resolving power of optical microscopy far beyond the diffraction limit (2-6), facilitating access to the organization of cells at the nanoscale by optical means. Although superresolution imaging of biological structures using labeled proteins has been well documented due to a wide range of methodologies that provide desirable labeling properties (7,8), and despite tremendous interest and demonstrated need, there are few nanoscopic methods to image macromolecular structures formed by nucleic acids due to constraints in labeling (9-14). Likewise, the limited techniques that currently exist cannot ...

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“…Introduction of higher level of detail can be achieved by the intermediate chain-of-beads approach, which involves two features: small-scale chromatin properties and overall genome organization based on experimental results, for example from Hi-C [165], FISH [168] or cryo-EM [159] Hi-C contacts) [171][172][173]. Constant improvement in Hi-C techniques [166] and the recent irruption of ultra-resolution fluorescence microscopy in the field [174] suggests that there is room for th 'int m diat ' a ach t improve thelevel of resolution, with the long-range objective to reach atleastnucleosome-level resolution. [176].…”

Section: Mesoscopic Studiesmentioning

confidence: 99%

Multiscale simulation of DNA

Dans¹,

Walther

Gómez

et al. 2016

Current Opinion in Structural Biology

135

123

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DNA is not only among the most important molecules in life, but a meeting point for biology, physics and chemistry, being studied by numerous techniques. Theoretical methods can help in gaining a detailed understanding of DNA structure and function, but their practical use is hampered by the multiscale nature of this molecule. In this regard, the study of DNA covers a broad range of different topics, from sub-Angstrom details of the electronic distributions of nucleobases, to the mechanical properties of millimeter-long chromatin fibers. Some of the biological processes involving DNA occur in femtoseconds, while others require years. In this review, we describe the most recent theoretical methods that have been considered to study DNA, from the electron to the chromosome, enriching our knowledge on this fascinating molecule.

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Chromatin Fibers Are Formed by Heterogeneous Groups of Nucleosomes In Vivo

Cited by 585 publications

References 53 publications

Transcription organizes euchromatin similar to an active microemulsion

Transcription organizes euchromatin similar to an active microemulsion

Superresolution intrinsic fluorescence imaging of chromatin utilizing native, unmodified nucleic acids for contrast

Multiscale simulation of DNA

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