scholarly journals Single particle trajectory statistic to reconstruct chromatin organization and dynamics

2019 ◽  
Author(s):  
O. Shukron ◽  
A. Seeber ◽  
A. Amitai ◽  
D. Holcman
Keyword(s):  
Single Particle ◽  
Chromatin Organization ◽  
Biophysical Parameters ◽  
Dna Damages ◽  
Chromatin Dynamics ◽  
Multiple Loci ◽  
Polymer Models ◽  
Dynamics And Function ◽  
And Function

AbstractChromatin organization remains complex and far from understood. We discuss here recent statistical methods to extract biophysical parameters from in vivo single particle trajectories of loci to reconstruct chromatin reorganization in response to cellular stress such as DNA damages. We look at the methods to analyze both single loci as well as multiple loci tracked simultaneously and explain how to quantify and describe chromatin motion using a combination of extractable parameters. These parameters can be converted into information about chromatin dynamics and function. Furthermore, we discuss how the time scale of recurrent motion of a locus can be extracted and converted into local chromatin dynamics. We also discuss the effect of various sampling rates on the estimated parameters. Finally, we discuss polymer methods based on cross-linkers that account for minimal loop constraints hidden in tracked loci, that reveal chromatin organization at the 250nmspatial scale. We list and refer to some algorithm packages that are now publicly available. To conclude, chromatin organization and dynamics at hundreds of nanometers can be reconstructed from locus trajectories and predicted based on polymer models.

scholarly journals Dynamics and Function of Langerhans Cells In Vivo

Immunity ◽  
2005 ◽  
Vol 22 (5) ◽  
pp. 643-654 ◽  
Author(s):  
Adrien Kissenpfennig ◽  
Sandrine Henri ◽  
Bertrand Dubois ◽  
Corinne Laplace-Builhé ◽  
Pierre Perrin ◽  
...  
Keyword(s):  
Langerhans Cells ◽  
Dynamics And Function ◽  
And Function

scholarly journals The function and dynamics of the apical scaffolding protein E3KARP are regulated by cell-cycle phosphorylation

2015 ◽  
Vol 26 (20) ◽  
pp. 3615-3627 ◽  
Author(s):  
Cécile Sauvanet ◽  
Damien Garbett ◽  
Anthony Bretscher
Keyword(s):  
Pdz Domain ◽  
Duplication Event ◽  
Scaffolding Protein ◽  
Gene Duplication Event ◽  
Pdz Domains ◽  
Tail Region ◽  
Dynamics And Function ◽  
And Function

We examine the dynamics and function of the apical scaffolding protein E3KARP/NHERF2, which consists of two PDZ domains and a tail containing an ezrin-binding domain. The exchange rate of E3KARP is greatly enhanced during mitosis due to phosphorylation at Ser-303 in its tail region. Whereas E3KARP can substitute for the function of the closely related scaffolding protein EBP50/NHERF1 in the formation of interphase microvilli, E3KARP S303D cannot. Moreover, the S303D mutation enhances the in vivo dynamics of the E3KARP tail alone, whereas in vitro the interaction of E3KARP with active ezrin is unaffected by S303D, implicating another factor regulating dynamics in vivo. A-Raf is found to be required for S303 phosphorylation in mitotic cells. Regulation of the dynamics of EBP50 is known to be dependent on its tail region but modulated by PDZ domain occupancy, which is not the case for E3KARP. Of interest, in both cases, the mechanisms regulating dynamics involve the tails, which are the most diverged region of the paralogues and probably evolved independently after a gene duplication event that occurred early in vertebrate evolution.

scholarly journals Single-molecule biophysics: at the interface of biology, physics and chemistry

2007 ◽  
Vol 5 (18) ◽  
pp. 15-45 ◽  
Author(s):  
Ashok A Deniz ◽  
Samrat Mukhopadhyay ◽  
Edward A Lemke
Keyword(s):  
Single Molecule ◽  
Biological Molecules ◽  
Single Molecule Fluorescence ◽  
Complex Behaviour ◽  
Single Molecule Biophysics ◽  
Single Molecule Studies ◽  
Dynamics And Function ◽  
And Function ◽  
Ensemble Experiments

Single-molecule methods have matured into powerful and popular tools to probe the complex behaviour of biological molecules, due to their unique abilities to probe molecular structure, dynamics and function, unhindered by the averaging inherent in ensemble experiments. This review presents an overview of the burgeoning field of single-molecule biophysics, discussing key highlights and selected examples from its genesis to our projections for its future. Following brief introductions to a few popular single-molecule fluorescence and manipulation methods, we discuss novel insights gained from single-molecule studies in key biological areas ranging from biological folding to experiments performed in vivo .

scholarly journals In Vivo Multicolor Imaging with Fluorescent Probes Revealed the Dynamics and Function of Osteoclast Proton Pumps

2019 ◽  
Vol 5 (6) ◽  
pp. 1059-1066 ◽  
Author(s):  
Masafumi Minoshima ◽  
Junichi Kikuta ◽  
Yuta Omori ◽  
Shigeto Seno ◽  
Riko Suehara ◽  
...  
Keyword(s):  
Fluorescent Probes ◽  
Proton Pumps ◽  
Multicolor Imaging ◽  
Dynamics And Function ◽  
And Function

scholarly journals The nuclear envelope protein Net39 is essential for muscle nuclear integrity and chromatin organization

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Andres Ramirez-Martinez ◽  
Yichi Zhang ◽  
Kenian Chen ◽  
Jiwoong Kim ◽  
Bercin K. Cenik ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nuclear Envelope ◽  
Envelope Protein ◽  
Transmembrane Protein ◽  
Chromatin Accessibility ◽  
Chromatin Organization ◽  
Potential Contribution ◽  
Molecular Etiology ◽  
And Function

AbstractLamins and transmembrane proteins within the nuclear envelope regulate nuclear structure and chromatin organization. Nuclear envelope transmembrane protein 39 (Net39) is a muscle nuclear envelope protein whose functions in vivo have not been explored. We show that mice lacking Net39 succumb to severe myopathy and juvenile lethality, with concomitant disruption in nuclear integrity, chromatin accessibility, gene expression, and metabolism. These abnormalities resemble those of Emery–Dreifuss muscular dystrophy (EDMD), caused by mutations in A-type lamins (LMNA) and other genes, like Emerin (EMD). We observe that Net39 is downregulated in EDMD patients, implicating Net39 in the pathogenesis of this disorder. Our findings highlight the role of Net39 at the nuclear envelope in maintaining muscle chromatin organization, gene expression and function, and its potential contribution to the molecular etiology of EDMD.

scholarly journals A transgenic toolkit for visualizing and perturbing microtubules in mice reveals unexpected functions for non-centrosomal arrays in epidermal morphogenesis

2017 ◽  
Author(s):  
Andrew Muroyama ◽  
Terry Lechler
Keyword(s):  
Cell Types ◽  
Microtubule Dynamics ◽  
Microtubule Organization ◽  
Strong Suppression ◽  
Physiological Functions ◽  
Microtubule Growth ◽  
Epidermal Morphogenesis ◽  
Dynamics And Function ◽  
And Function

AbstractDifferentiation induces reorganization of microtubules (MTs) into non-centrosomal arrays in a variety of tissues. The physiological functions of these microtubule arrays are just beginning to be understood as few tools currently exist to genetically perturb microtubule organization in vivo, particularly in mammals. We developed a genetic toolkit that can be broadly applied to the study of microtubule dynamics and function in many cell types. Using a TRE-EB1-GFP mouse we demonstrate that distinct differentiation transitions in the epidermis cause a decrease in microtubule growth rates and microtubule growth lifetimes, resulting in strong suppression of dynamics. To understand the physiological functions of these stable, non-centrosomal microtubules, we generated a TRE-spastin mouse, which can be used to perturb microtubule organization in a wide-variety of tissues in vivo. Unexpectedly, microtubule perturbation exclusively in post-mitotic keratinocytes had profound consequences on epidermal morphogenesis. We uncoupled novel cell-autonomous roles for MTs in differentiation-driven cell flattening from non-cell autonomous functions in regulating proliferation, differentiation, and tissue architecture. Taken together, we have created tools that will be broadly useful for the study of microtubule dynamics and function in mammalian tissue physiology and have used them to uncover previously unknown functions for non-centrosomal microtubules during mammalian epidermal development.

scholarly journals Polymer physics of nuclear organization and function

2016 ◽  
Author(s):  
A. Amitai ◽  
D. Holcman
Keyword(s):  
Nuclear Organization ◽  
Gene Activation ◽  
Physical Models ◽  
Biophysical Parameters ◽  
Theoretical Approaches ◽  
Search Mechanism ◽  
Polymer Models ◽  
Or Gene ◽  
Microscopy Data ◽  
And Function

AbstractWe review here recent progress to link the nuclear organization to its function, based on elementary physical processes such as diffusion, polymer dynamics of DNA, chromatin and the search mechanism for a small target by double-stranded DNA (dsDNA) break. These physical models and their analysis make it possible to compute critical rates involved in cell reorganization timing, which depends on many parameters. In the framework of polymer models, various empirical observations are interpreted as anomalous diffusion of chromatin at various time scales. The reviewed theoretical approaches offer a framework for extracting features, biophysical parameters, predictions, and so on, based on a large variety of experimental data, such as chromosomal capture data, single particle trajectories, and more. Combining theoretical approaches with live cell microscopy data should unveil some of the still unexplained behavior of the nucleus in carrying out some of its key function involved in survival, DNA repair or gene activation.

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