scholarly journals Topology, structures, and energy landscapes of human chromosomes

2015 ◽  
Vol 112 (19) ◽  
pp. 6062-6067 ◽  
Author(s):  
Bin Zhang ◽  
Peter G. Wolynes
Keyword(s):  
Liquid Crystalline ◽  
Spatial Organization ◽  
Human Chromosomes ◽  
Energy Landscapes ◽  
Interphase Chromosome ◽  
Chromosome Conformation ◽  
Information Theoretic ◽  
Knot Invariants ◽  
Topologically Associating Domains ◽  
And Topology

Chromosome conformation capture experiments provide a rich set of data concerning the spatial organization of the genome. We use these data along with a maximum entropy approach to derive a least-biased effective energy landscape for the chromosome. Simulations of the ensemble of chromosome conformations based on the resulting information theoretic landscape not only accurately reproduce experimental contact probabilities, but also provide a picture of chromosome dynamics and topology. The topology of the simulated chromosomes is probed by computing the distribution of their knot invariants. The simulated chromosome structures are largely free of knots. Topologically associating domains are shown to be crucial for establishing these knotless structures. The simulated chromosome conformations exhibit a tendency to form fibril-like structures like those observed via light microscopy. The topologically associating domains of the interphase chromosome exhibit multistability with varying liquid crystalline ordering that may allow discrete unfolding events and the landscape is locally funneled toward “ideal” chromosome structures that represent hierarchical fibrils of fibrils.

scholarly journals A chromosome folding intermediate at the condensin-to-cohesin transition during telophase

2019 ◽  
Author(s):  
Kristin Abramo ◽  
Anne-Laure Valton ◽  
Sergey V. Venev ◽  
Hakan Ozadam ◽  
A. Nicole Fox ◽  
...  
Keyword(s):  
Mitotic Chromosome ◽  
Chromatin Binding ◽  
Folding Intermediate ◽  
Binding Assays ◽  
Interphase Chromosome ◽  
Chromosome Conformation ◽  
Topologically Associating Domains ◽  
Late Telophase ◽  
Nested Loop ◽  
Inactive Chromatin

SummaryChromosome folding is extensively modulated as cells progress through the cell cycle. During mitosis, condensin complexes fold chromosomes in helically arranged nested loop arrays. In interphase, the cohesin complex generates loops that can be stalled at CTCF sites leading to positioned loops and topologically associating domains (TADs), while a separate process of compartmentalization drives the spatial segregation of active and inactive chromatin domains. We used synchronized cell cultures to determine how the mitotic chromosome conformation is transformed into the interphase state. Using Hi-C, chromatin binding assays, and immunofluorescence we show that by telophase condensin-mediated loops are lost and a transient folding intermediate devoid of most loops forms. By late telophase, cohesin-mediated CTCF-CTCF loops and positions of TADs start to emerge rapidly. Compartment boundaries are also established in telophase, but long-range compartmentalization is a slow process and proceeds for several hours after cells enter G1. Our results reveal the kinetics and order of events by which the interphase chromosome state is formed and identify telophase as a critical transition between condensin and cohesin driven chromosome folding.

Chromosome interactome inferred from mitosis-G1 transition

2016 ◽  
Author(s):  
Y.A. Eidelman ◽  
S.V. Slanina ◽  
A.V. Aleshchenko ◽  
S.G. Andreev
Keyword(s):  
Spatial Organization ◽  
Contact Map ◽  
Interphase Chromosome ◽  
Basic Principles ◽  
Chromosome Conformation ◽  
3D Genome ◽  
Contact Patterns ◽  
Genome Wide ◽  
Genome Study ◽  
Contact Data

ABSTRACTThe progress in experimental techniques aimed at 3D genome study is yet to bring about revelation of basic principles of genome folding. Chromosome conformation capture Hi-C technologies provide genome wide mapping of genomic loci interactions but spatial organization of chromosomes remains unknown. Here, we develop a polymer modeling approach to generate the ensemble of 3D chromosome conformations for mapping genetic loci contacts and the positions of megabase chromosomal domains in interphase chromosome at different time of mitosis-interphase transition. We demonstrate that (*) whole chromosome contact map (interactome) generated for mouse chromosome 18 structure and (**) contact patterns, observed soon after mitotic decondensation and remaining similar during G1, correlate well with the experimental Hi-C contact data. The results suggest that contact map formation and spatial compartmentalization of an interphase chromosome are driven by interactions between different types of domains during formation of globular chromosome state at the end of mitotis-G1 transition.

scholarly journals Shape Transitions and Chiral Symmetry Breaking in the Energy Landscape of the Mitotic Chromosome

2015 ◽  
Author(s):  
Bin Zhang ◽  
Peter Wolynes
Keyword(s):  
Symmetry Breaking ◽  
Chiral Symmetry ◽  
Liquid Crystalline ◽  
Chiral Symmetry Breaking ◽  
Energy Landscape ◽  
Interaction Strength ◽  
Cylindrical Shape ◽  
Interphase Chromosome ◽  
Information Theoretic ◽  
Dynamical Simulations

We derive an unbiased information theoretic energy landscape for chromosomes at metaphase using a maximum entropy approach that accurately reproduces the details of the experimentally measured pair-wise contact probabilities between genomic loci. Dynamical simulations using this landscape lead to cylindrical, helically twisted structures reflecting liquid crystalline order. These structures are similar to those arising from a generic ideal homogenized chromosome energy landscape. The helical twist can be either right or left handed so chiral symmetry is broken spontaneously. The ideal chromosome landscape when augmented by interactions like those leading to topologically associating domain (TAD) formation in the interphase chromosome reproduces these behaviors. The phase diagram of this landscape shows the helical fiber order and the cylindrical shape persist at temperatures above the onset of chiral symmetry breaking which is limited by the TAD interaction strength.

scholarly journals OnTAD: hierarchical domain structure reveals the divergence of activity among TADs and boundaries

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Lin An ◽  
Tao Yang ◽  
Jiahao Yang ◽  
Johannes Nuebler ◽  
Guanjue Xiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Domain Structure ◽  
High Frequency ◽  
Spatial Organization ◽  
Structural Units ◽  
Regulatory Interactions ◽  
Link Type ◽  
Topologically Associating Domains

AbstractThe spatial organization of chromatin in the nucleus has been implicated in regulating gene expression. Maps of high-frequency interactions between different segments of chromatin have revealed topologically associating domains (TADs), within which most of the regulatory interactions are thought to occur. TADs are not homogeneous structural units but appear to be organized into a hierarchy. We present OnTAD, an optimized nested TAD caller from Hi-C data, to identify hierarchical TADs. OnTAD reveals new biological insights into the role of different TAD levels, boundary usage in gene regulation, the loop extrusion model, and compartmental domains. OnTAD is available at https://github.com/anlin00007/OnTAD.

scholarly journals Large-scale chromatin structure of inducible genes: transcription on a condensed, linear template

2009 ◽  
Vol 185 (1) ◽  
pp. 87-100 ◽  
Author(s):  
Yan Hu ◽  
Igor Kireev ◽  
Matt Plutz ◽  
Nazanin Ashourian ◽  
Andrew S. Belmont
Keyword(s):  
Chromatin Structure ◽  
Transcriptional Activation ◽  
Large Scale ◽  
Nuclear Speckles ◽  
Interphase Chromosome ◽  
Chromosome Conformation ◽  
Dynamic Events ◽  
Classical Models ◽  
Chromatin Fibers

The structure of interphase chromosomes, and in particular the changes in large-scale chromatin structure accompanying transcriptional activation, remain poorly characterized. Here we use light microscopy and in vivo immunogold labeling to directly visualize the interphase chromosome conformation of 1–2 Mbp chromatin domains formed by multi-copy BAC transgenes containing 130–220 kb of genomic DNA surrounding the DHFR, Hsp70, or MT gene loci. We demonstrate near-endogenous transcription levels in the context of large-scale chromatin fibers compacted nonuniformly well above the 30-nm chromatin fiber. An approximately 1.5–3-fold extension of these large-scale chromatin fibers accompanies transcriptional induction and active genes remain mobile. Heat shock–induced Hsp70 transgenes associate with the exterior of nuclear speckles, with Hsp70 transcripts accumulating within the speckle. Live-cell imaging reveals distinct dynamic events, with Hsp70 transgenes associating with adjacent speckles, nucleating new speckles, or moving to preexisting speckles. Our results call for reexamination of classical models of interphase chromosome organization.

scholarly journals Cohesin disrupts polycomb-dependent chromosome interactions

2019 ◽  
Author(s):  
JDP Rhodes ◽  
A Feldmann ◽  
B Hernández-Rodríguez ◽  
N Díaz ◽  
JM Brown ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
Gene Repression ◽  
Chromosome Conformation ◽  
Regulate Gene Expression ◽  
Topologically Associating Domains ◽  
Chromosome Organisation ◽  
Regulate Gene

AbstractHow chromosome organisation is related to genome function remains poorly understood. Cohesin, loop-extrusion, and CTCF have been proposed to create structures called topologically associating domains (TADs) to regulate gene expression. Here, we examine chromosome conformation in embryonic stem cells lacking cohesin and find as in other cell types that cohesin is required to create TADs and regulate A/B compartmentalisation. However, in the absence of cohesin we identify a series of long-range chromosomal interactions that persist. These correspond to regions of the genome occupied by the polycomb repressive system, depend on PRC1, and we discover that cohesin counteracts these interactions. This disruptive activity is independent of CTCF and TADs, and regulates gene repression by the polycomb system. Therefore, in contrast to the proposal that cohesin creates structure in chromosomes, we discover a new role for cohesin in disrupting polycomb-dependent chromosome interactions to regulate gene expression.

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