scholarly journals Genome organization via loop extrusion, insights from polymer physics models

2019 ◽  
Vol 19 (2) ◽  
pp. 119-127 ◽  
Author(s):  
Surya K Ghosh ◽  
Daniel Jost

Abstract Understanding how genomes fold and organize is one of the main challenges in modern biology. Recent high-throughput techniques like Hi-C, in combination with cutting-edge polymer physics models, have provided access to precise information on 3D chromosome folding to decipher the mechanisms driving such multi-scale organization. In particular, structural maintenance of chromosome (SMC) proteins play an important role in the local structuration of chromatin, putatively via a loop extrusion process. Here, we review the different polymer physics models that investigate the role of SMCs in the formation of topologically associated domains (TADs) during interphase via the formation of dynamic loops. We describe the main physical ingredients, compare them and discuss their relevance against experimental observations.

2019 ◽  
Vol 5 (5) ◽  
pp. eaaw5294 ◽  
Author(s):  
Shuai Wu ◽  
Nail Fatkhutdinov ◽  
Leah Rosin ◽  
Jennifer M. Luppino ◽  
Osamu Iwasaki ◽  
...  

ARID1A, a subunit of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex, localizes to both promoters and enhancers to influence transcription. However, the role of ARID1A in higher-order spatial chromosome partitioning and genome organization is unknown. Here, we show that ARID1A spatially partitions interphase chromosomes and regulates higher-order genome organization. The SWI/SNF complex interacts with condensin II, and they display significant colocalizations at enhancers. ARID1A knockout drives the redistribution of condensin II preferentially at enhancers, which positively correlates with changes in transcription. ARID1A and condensin II contribute to transcriptionally inactive B-compartment formation, while ARID1A weakens the border strength of topologically associated domains. Condensin II redistribution induced by ARID1A knockout positively correlates with chromosome sizes, which negatively correlates with interchromosomal interactions. ARID1A loss increases the trans interactions of small chromosomes, which was validated by three-dimensional interphase chromosome painting. These results demonstrate that ARID1A is important for large-scale genome folding and spatially partitions interphase chromosomes.


Author(s):  
E. M. Ratnikov ◽  
D. O. Milko

Annotation Purpose. Development of a program and methods for conducting experimental studies of the extrusion process with the definition of parameters and modes of operation of the extruder to improve its energy performance. Methods. Methods of mathematical statistics, synthesis, analysis, description and modeling were used. Results. The application of mathematical methods, in particular mathematical planning, reduces the number of experiments several times, and allows to evaluate the role of influencing factors, obtain a mathematical model of the process and determine the optimal conditions for its parameters and modes, etc. Conclusions. The methodology for experimental studies of a screw extruder is presented with the necessary equipment and methodology for processing the obtained experimental data. A mathematical method of planning, which reduces the number of experiments several times, allows us to evaluate the role of factors affecting productivity and energy intensity is presented. Keywords: extruder, auger, nutrients, research methodology, extrusion, processing, feed.


2021 ◽  
Vol 129 (12) ◽  
pp. 125102
Author(s):  
A. S. Saleh ◽  
H. Ceric ◽  
H. Zahednamesh
Keyword(s):  

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Benjamin Soibam ◽  
Ayzhamal Zhamangaraeva

Abstract Background Chromosomes are organized into units called topologically associated domains (TADs). TADs dictate regulatory landscapes and other DNA-dependent processes. Even though various factors that contribute to the specification of TADs have been proposed, the mechanism is not fully understood. Understanding the process for specification and maintenance of these units is essential in dissecting cellular processes and disease mechanisms. Results In this study, we report a genome-wide study that considers the idea of long noncoding RNAs (lncRNAs) mediating chromatin organization using lncRNA:DNA triplex-forming sites (TFSs). By analyzing the TFSs of expressed lncRNAs in multiple cell lines, we find that they are enriched in TADs, their boundaries, and loop anchors. However, they are evenly distributed across different regions of a TAD showing no preference for any specific portions within TADs. No relationship is observed between the locations of these TFSs and CTCF binding sites. However, TFSs are located not just in promoter regions but also in intronic, intergenic, and 3’UTR regions. We also show these triplex-forming sites can be used as predictors in machine learning models to discriminate TADs from other genomic regions. Finally, we compile a list of important “TAD-lncRNAs” which are top predictors for TADs identification. Conclusions Our observations advocate the idea that lncRNA:DNA TFSs are positioned at specific areas of the genome organization and are important predictors for TADs. LncRNA:DNA triplex formation most likely is a general mechanism of action exhibited by some lncRNAs, not just for direct gene regulation but also to mediate 3D chromatin organization.


2018 ◽  
Vol 85 ◽  
pp. 299-310 ◽  
Author(s):  
An Thi-Binh Nguyen ◽  
Michaël Nigen ◽  
Luciana Jimenez ◽  
Hassina Ait-Abderahim ◽  
Charles Cunault ◽  
...  

2017 ◽  
Vol 43 (3) ◽  
pp. 213-232 ◽  
Author(s):  
M. Haghi Kashani ◽  
A. Hosseini ◽  
F. Sassani ◽  
F. K. Ko ◽  
A. S. Milani

2021 ◽  
Vol 134 (1) ◽  
pp. jcs247577
Author(s):  
Avi Matityahu ◽  
Itay Onn

ABSTRACTThe three-dimensional structure of chromatin is determined by the action of protein complexes of the structural maintenance of chromosome (SMC) family. Eukaryotic cells contain three SMC complexes, cohesin, condensin, and a complex of Smc5 and Smc6. Initially, cohesin was linked to sister chromatid cohesion, the process that ensures the fidelity of chromosome segregation in mitosis. In recent years, a second function in the organization of interphase chromatin into topologically associated domains has been determined, and loop extrusion has emerged as the leading mechanism of this process. Interestingly, fundamental mechanistic differences exist between mitotic tethering and loop extrusion. As distinct molecular switches that aim to suppress loop extrusion in different biological contexts have been identified, we hypothesize here that loop extrusion is the default biochemical activity of cohesin and that its suppression shifts cohesin into a tethering mode. With this model, we aim to provide an explanation for how loop extrusion and tethering can coexist in a single cohesin complex and also apply it to the other eukaryotic SMC complexes, describing both similarities and differences between them. Finally, we present model-derived molecular predictions that can be tested experimentally, thus offering a new perspective on the mechanisms by which SMC complexes shape the higher-order structure of chromatin.


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