Current theoretical models fail to predict the topological complexity of the human genome

Frontiers in Molecular Biosciences
Javier ArsuagaMariel Vazquez

Abstract

Understanding the folding of the human genome is a key challenge of modern structural biology. The emergence of chromatin conformation capture assays (e.g., Hi-C) has revolutionized chromosome biology and provided new insights into the three dimensional structure of the genome. The experimental data are highly complex and need to be analyzed with quantitative tools. It has been argued that the data obtained from Hi-C assays are consistent with a fractal organization of the genome. A key characteristic of the fractal globule is the lack of topological complexity (knotting or inter-linking). However, the absence of topological complexity contradicts results from polymer physics showing that the entanglement of long linear polymers in a confined volume increases rapidly with the length and with decreasing volume. In vivo and in vitro assays support this claim in some biological systems. We simulate knotted lattice polygons confined inside a sphere and demonstrate that their contact frequencies agree with the human Hi-C data. We conclude that the topological complexity of the human genome cannot be inferred from current Hi-C data.

References

May 1, 1991·Trends in Genetics : TIG·P Borst
Sep 25, 1985·Nucleic Acids Research·J S WolfsonM N Swartz
Mar 28, 1971·Journal of Molecular Biology·L Simpson, A Da Silva
Sep 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·L F LiuJ C Wang
Jan 15, 1999·Journal of Molecular Biology·C MünkelJ Langowski
Mar 4, 2000·Proceedings of the National Academy of Sciences of the United States of America·V F Holmes, N R Cozzarelli
Feb 16, 2002·Science·Job DekkerNancy Kleckner
Apr 18, 2002·Proceedings of the National Academy of Sciences of the United States of America·Javier ArsuagaJoaquim Roca
Nov 22, 2002·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Miyuki K Shimamura, Tetsuo Deguchi
Jun 17, 2005·Proceedings of the National Academy of Sciences of the United States of America·Javier ArsuagaJoaquim Roca
Oct 27, 2005·Journal of the American Chemical Society·Peter VirnauMehran Kardar
Feb 18, 2006·The Journal of Chemical Physics·C MichelettiD W Summers
Mar 16, 2007·Nature Reviews. Cancer·Felix MitelmanFredrik Mertens
Aug 30, 2008·PLoS Computational Biology·Angelo Rosa, Ralf Everaers
Feb 28, 2009·Journal of Cellular Biochemistry·Melissa J Fullwood, Yijun Ruan
Apr 10, 2010·Journal of Mathematical Biology·T BlackstoneJ Arsuaga
Nov 24, 2011·Physical Review Letters·Luca TubianaCristian Micheletti
Sep 19, 2012·Proceedings of the National Academy of Sciences of the United States of America·Mariano BarbieriMario Nicodemi
Mar 22, 2013·Biochemical Society Transactions·Reuben BrasherMariel Vazquez
Nov 8, 2013·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Zhizhuo ZhangWing-Kin Sung
Feb 13, 2014·Biostatistics·Mark R SegalJavier Arsuaga

❮ Previous
Next ❯

Citations

May 3, 2019·Scientific Reports·Maxime PouokamJavier Arsuaga
Apr 10, 2019·Polymers·Dusan RackoAndrzej Stasiak
Oct 1, 2017·Scientific Reports·Robert StolzMariel Vazquez
Dec 11, 2019·Biophysical Journal·Dimos GoundaroulisAndrzej Stasiak
Jul 3, 2021·Cells·Jekaterina ErenpreisaAlessandro Giuliani
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Andreas HankeStephen D Levene

❮ Previous
Next ❯

Datasets Mentioned

BETA
GM
007067

Methods Mentioned

BETA
Hi-C

Software Mentioned

matlab
BFACF
Knotplot

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.