Bulletin of the American Physical Society
APS March Meeting 2021
Volume 66, Number 1
Monday–Friday, March 15–19, 2021; Virtual; Time Zone: Central Daylight Time, USA
Session V14: Physics of Genome Organization IIFocus Live
|
Hide Abstracts |
Sponsoring Units: DBIO Chair: Bin Zhang, Massachusetts Institute of Technology; Alexandre Morozov, Rutgers University, New Brunswick |
Thursday, March 18, 2021 3:00PM - 3:12PM Live |
V14.00001: Learning the distribution of single-cell chromosome conformations in bacteria reveals emergent order across genomic scales Joris Messelink, Muriel van Teeseling, Jacqueline Janssen, Martin Thanbichler, Chase Broedersz The order and variability of bacterial chromosome organization, contained within the distribution of chromosome conformations, are unclear. We develop a fully data-driven maximum entropy approach to extract single-cell 3D chromosome conformations from Hi-C experiments on the model organism Caulobacter crescentus. The predictive power of our model is validated by independent experiments. We find that on large genomic scales, organizational features are predominantly present along the long cell axis: chromosomal loci exhibit striking long-ranged two-point axial correlations, indicating emergent order. This organization is associated with large genomic clusters we term Super Domains (SuDs), whose existence we support with super-resolution microscopy. On smaller genomic scales, our model reveals chromosome extensions that correlate with transcriptional and loop extrusion activity. Finally, we quantify the information contained in chromosome organization that may guide cellular processes. Our approach can be extended to other species, providing a general strategy to resolve variability in single-cell chromosomal organization. |
Thursday, March 18, 2021 3:12PM - 3:24PM Live |
V14.00002: Structural and Dynamical Signatures of Local DNA Damage in Live Cells Jonah Eaton, Alexandra Zidovska The dynamic organization of chromatin inside the cell nucleus plays a key role in gene regulation and maintaining genome integrity. While the static folded state of the genome has been studied before, the dynamical signatures of processes such as transcription or DNA repair are unknown. We investigate the interphase chromatin dynamics in human cells in response to local damage, DNA double strand breaks (DSBs), by monitoring the DSB dynamics and the compaction of the surrounding chromatin in live cells. We find DSBs to possess a unique chromatin compaction profile, while being more mobile when located in the nuclear interior as opposed to the periphery. We show that DSB motion is subdiffusive, ATP-dependent, and exhibits unique dynamical signatures compared to undamaged chromatin. We find that DSB mobility follows a universal relationship based on the local environment suggesting that the repair processes are robust and likely deterministic. Such knowledge may help in detection of DNA damage in live cells and aid our biophysical understanding of genome integrity in health and disease [Eaton & Zidovska, Biophys. J., 2020]. |
Thursday, March 18, 2021 3:24PM - 3:36PM Live |
V14.00003: Mapping the organization of Esherichia Coli Chromosome in a HI-C integrated model Jagannath Mondal, Abdul Wasim, Ankit Gupta The chromosome of Escherichia Coli (E. coli) is riddled with multi-faceted complexity and its nature of organization is slowly getting recognised. The emergence of chromosome conformation capture techniques and super-resolution microscopy are providing newer ways to explore chromosome organization, and dynamics and its effect on gene expression. In the seminar we will present a model where we combine a beads-on-a-spring polymer-based framework with recently reported high-resolution Hi-C data of E. coli chromosome to develop a comprehensive model of E. coli chromosome at 5 kilo base-pair resolution. The model captures a self-organised chromosome composed of linearly organised genetic loci, and segregated macrodomains within a ring-like helicoid architecture, with no net chirality. Additionally, a genome-wide map identifies multiple chromosomal interaction domains (CIDs) and corroborates well with a transcription-centric model of the E. coli chromosome. The investigation further demonstrates that while only a small fraction of the Hi-C contacts is dictating the underlying chromosomal organization, a random-walk polymer chain devoid of Hi-C encoded contact information would fail to map the key genomic interactions unique to E. coli. |
Thursday, March 18, 2021 3:36PM - 3:48PM Live |
V14.00004: The influence of transcription in nucleosome positioning Zhongling Jiang, Bin Zhang Nucleosome positioning plays an important role in genome's function by restricting the DNA accessibility and incorporating regulatory factors. Although the role of DNA sequence in positioning nucleosomes has been widely studied, the understanding of the impact of transcription remains limited due to the complicated factors involved in this non-equilibrium process. Through numerical simulations, we investigated the influence of DNA sequence specificity, transcription factor binding, enzyme remodeling, and Pol II elongation in nucleosome positioning across species near the transcription start site (TSS). By exploring the effect of each factor, we found that a tug-of-war between two types of remodeling enzymes can reconcile the seemingly conflicting nucleosome density profiles at varying transcription levels observed in yeast and mouse embryonic stem cells. |
Thursday, March 18, 2021 3:48PM - 4:00PM Live |
V14.00005: Theoretical study of chromatin organization at the mesoscale Omar Adame-Arana, Gaurav Bajpai, Samuel Safran Recent experiments on chromatin of muscle nuclei in intact organisms, have shown that chromatin may organize peripherally with chromatin depleted regions in the center of the nucleus, challenging the conventional picture in which chromatin fills the entire nuclear envelope. Furthermore, polymer simulations offer a plausible explanation for such chromatin organization, suggesting that it stems from an interplay between chromatin self-attraction and its interactions with the nuclear lamina (NL) via the lamin-associated domains (LAD) of the chromatin. Motivated by these findings, we provide analytical insight using two complementary approaches. On the one hand, we predict the chromatin concentration profiles using a mean-field polymer model in which we account for the bonding interaction between LAD and the NL. On the other hand, we model chromatin as a liquid droplet and study the transitions between different types of chromatin organization at the mesoscale as a function of the droplet surface tension, the LAD fraction of the chromatin, and their interaction strength with the NL. Comparison of our analytical predictions with Brownian dynamical simulations, demonstrate the roles of surface tension and the lamina interaction in determining the nuclear-scale chromatin organization. |
Thursday, March 18, 2021 4:00PM - 4:12PM Live |
V14.00006: Exploring coupled epigenetic and genetic switches with variational methods Amogh Sood, Bin Zhang For eukaryotes, gene regulation is intimately linked to epigenetic modifications such as histone marks and corresponding change in nucleosome structure. In this work, we introduce a minimal kinetic model for gene regulation that accounts for the impact of histone modifications on protein production by a self-activating gene. We develop an analytical approach using the variational method, a useful approximation scheme, to study the exact master equation in a second quantized framework. Following our previous work wherein we exploited the symmetry of SU(2) operators to construct the action for an isolated epigenetic switch, we once again utilize the connection between SU(n) operators and probability distributions to arrive at a generalized variational ansatz that allows us to treat the coupled genetic and epigenetic switches. The emerging epigenetic landscape captures the delicate interplay between transcription factors and epigenetic regulation vis-à-vis histone modifications. We notice that by changing a single parameter, and quenching the noise in the epigenetic system, we are able to induce switching behaviour in the coupled system. |
Thursday, March 18, 2021 4:12PM - 4:24PM Live |
V14.00007: Plasticity of genome structure and organization governed by the differential activity of SMC complexes Sumitabha Brahmachari, Vinicius G. Contessoto, Michele Di Pierro, Jose N Onuchic Understanding the role of SMC (Structural Maintenance of Chromosomes) complexes in organizing the genome has been a long-standing research avenue. Recent experiments studying chromosome architecture following the depletion of various SMC complexes have uncovered a number of phenotypic variants. Here, we adopt an energy-landscape-based polymer model of chromosomes that features SMC-driven linear compaction as an externally controllable degree of freedom. The linear compaction potential, also called the 'ideal chromosome', is further decomposed into short- and long-range components, associated with the activity of SMC variants like condensins and cohesin. As we modulate the relative intensity of short- versus long-range linear compaction, we find the emergence of structural phenotypes, such as chromosome territories and spatially clustered centromeres. These structural phenotypes highlight plasticity in the genome architecture that is directly associated with the differential activity of SMC variants. Our model helps rationalize both the SMC-depletion experiments, and aspects of genome architecture across the evolutionary tree featuring species lacking certain SMC variants. |
Thursday, March 18, 2021 4:24PM - 4:36PM Live |
V14.00008: Homolog locus pairing is a transient, diffusion-mediated process in meiotic prophase Bruno Beltran, Trent Newman, Sean Burgess, Andrew Spakowitz The pairing of homologous chromosomes in meiosis I is essential for sexual reproduction, yet pairing dynamics at individual homologous loci remain largely uncharacterized. We track individual homologous locus pairs at various stages of meiosis. We observe mean squared change in displacements (MSCDs) that exhibit the t^(1/2) power-law scaling behavior characteristic of polymer diffusion followed by a plateau-from which we can infer that homologous loci are weakly tethered to each other. We develop a theory for Rouse polymers with ``homologous'' linkages, and show that the plateau behavior is consistent with a handful of randomly-spaced linkages per chromosome forming over the course of meiosis. Brownian dynamics simulations of our linked polymers quantitatively reproduce the search times and pairing lifetimes observed at each successive stage of meiosis. These results suggest that homolog pairing is driven purely by chromatin diffusion, and that the DSB-dependence of homolog pairing comes not from the tagged loci experiencing DSBs, but instead from distal homologous linkages along the chromosome. |
Thursday, March 18, 2021 4:36PM - 4:48PM Live |
V14.00009: Chromatin Structure and Activity Modifies Dynamics and Interactions Giada Forte, Chris Brackley, Nick Gilbert, Davide Marenduzzo The static structure of geni loci can now be investigated by 3C experiments [1] and computer simulations [2]. Yet, the loci dynamics is far less understood and much more difficult to investigate experimentally. |
Thursday, March 18, 2021 4:48PM - 5:00PM Live |
V14.00010: Fibration symmetries uncover the building blocks of biological networks Ian Leifer, Flaviano Morone, Hernan Makse The success of symmetries in explaining the physical world, from general relativity to the standard model of particle physics and all phases of matter, raises the question of why the same concept could not be equally applied to explain emergent properties of biological systems. |
Thursday, March 18, 2021 5:00PM - 5:36PM Live |
V14.00011: On the Border of Order: Chromosomal Organization in Space and Time Invited Speaker: Olga Dudko Many processes in biology, from antibody production to tissue differentiation, share a common fundamental step — establishing physical contact between distant genomic segments. A key outstanding question is then: How do genomic segments that are strung out over millions of base pairs along the DNA find each other in the crowded cell on a remarkably short timescale? This question, fundamental to biology, can be recognized as the physics problem of the first-passage time. We show how concepts from statistical physics help reveal the physical principles by which cells solve this first-passage problem with astonishing efficiency. We illustrate these ideas in the context of adaptive immunity – the system that enables the individual to respond to a great variety of pathogens through a diverse repertoire of antibodies. |
Thursday, March 18, 2021 5:36PM - 5:48PM Live |
V14.00012: Centromeres and Telomeres as Rheological Probes of the Human Nucleus Alexis Clavijo, Steven Ionov, Alexandra Zidovska The nucleus of eukaryotic cells stores genetic information in chromatin, the functional form of DNA in cells. Chromatin loci have been observed to exhibit anomalous motion that is often ascribed to the viscoelastic nature of the chromatin, transient interactions of DNA-associated proteins and/or physical obstructions [1,2]. However, a direct link between a chromatin locus motion and the rheology of its local environment is missing. In this work, we investigate dynamics of specific genomic loci, centromeres and telomeres, the centers and ends of the linear interphase chromosomes, respectively, in the context of their local rheological environment. Using simultaneous two-color spinning disc confocal microscopy combined with recently developed machine-learning-assisted tracking algorithms [3], we monitor the motion of telomeres and centromeres in live human cells and extract the rheological properties of their surrounding environment, mapping the chromatin rheology across the cell nucleus. |
Thursday, March 18, 2021 5:48PM - 6:00PM Live |
V14.00013: Noninvasive Measurement of Interphase Chromatin Rheology In Vivo Iraj Eshghi, Jonah Eaton, Alexandra Zidovska Material properties of the genome are critical for its proper function and organization inside the cell nucleus. Chromatin, the functional form of DNA in cells, consists of DNA and associated proteins, forming long linear fibers in the interphase nucleus of eukaryotic cells. Traditionally, rheology of cellular components has been studied by tracking microparticles injected inside the cell [1]. Recently, we developed an injection-free noninvasive approach to study chromatin rheology using nuclear organelles as native probes [2]. Here, we show an alternative noninvasive experimental strategy using intrinsic dynamics to measure chromatin rheology across a large range of timescales, and elucidate the viscoelastic nature of chromatin in live cells. The measured rheology is captured by a surprisingly simple model whose few parameters have clear physical interpretations for this complex active material. |
Follow Us |
Engage
Become an APS Member |
My APS
Renew Membership |
Information for |
About APSThe American Physical Society (APS) is a non-profit membership organization working to advance the knowledge of physics. |
© 2024 American Physical Society
| All rights reserved | Terms of Use
| Contact Us
Headquarters
1 Physics Ellipse, College Park, MD 20740-3844
(301) 209-3200
Editorial Office
100 Motor Pkwy, Suite 110, Hauppauge, NY 11788
(631) 591-4000
Office of Public Affairs
529 14th St NW, Suite 1050, Washington, D.C. 20045-2001
(202) 662-8700