Mechanical properties of symmetric and asymmetric DNA A-tracts: implications for looping and nucleosome positioning

A-tracts are functionally important DNA sequences which induce helix bending and have peculiar structural properties. While A-tract structure has been qualitatively well characterized, their mechanical properties remain controversial. A-tracts appear structurally rigid and resist nucleosome formatio...

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Main Authors:	Dršata, Tomáš, Špačková, Naďa, Jurečka, Petr, Zgarbová, Marie, Šponer, Jiří, Lankaš, Filip
Format:	Online
Language:	English
Published:	Oxford University Press 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066768/

id	pubmed-4066768
recordtype	oai_dc
spelling	pubmed-40667682014-06-24 Mechanical properties of symmetric and asymmetric DNA A-tracts: implications for looping and nucleosome positioning Dršata, Tomáš Špačková, Naďa Jurečka, Petr Zgarbová, Marie Šponer, Jiří Lankaš, Filip Structural Biology A-tracts are functionally important DNA sequences which induce helix bending and have peculiar structural properties. While A-tract structure has been qualitatively well characterized, their mechanical properties remain controversial. A-tracts appear structurally rigid and resist nucleosome formation, but seem flexible in DNA looping. In this work, we investigate mechanical properties of symmetric AnTn and asymmetric A2n tracts for n = 3, 4, 5 using two types of coarse-grained models. The first model represents DNA as an ensemble of interacting rigid bases with non-local quadratic deformation energy, the second one treats DNA as an anisotropically bendable and twistable elastic rod. Parameters for both models are inferred from microsecond long, atomic-resolution molecular dynamics simulations. We find that asymmetric A-tracts are more rigid than the control G/C-rich sequence in localized distortions relevant for nucleosome formation, but are more flexible in global bending and twisting relevant for looping. The symmetric tracts, in contrast, are more rigid than asymmetric tracts and the control, both locally and globally. Our results can reconcile the contradictory stiffness data on A-tracts and suggest symmetric A-tracts to be more efficient in nucleosome exclusion than the asymmetric ones. This would open a new possibility of gene expression manipulation using A-tracts. Oxford University Press 2014-07-01 2014-05-28 /pmc/articles/PMC4066768/ /pubmed/24829460 http://dx.doi.org/10.1093/nar/gku338 Text en © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Dršata, Tomáš Špačková, Naďa Jurečka, Petr Zgarbová, Marie Šponer, Jiří Lankaš, Filip
spellingShingle	Dršata, Tomáš Špačková, Naďa Jurečka, Petr Zgarbová, Marie Šponer, Jiří Lankaš, Filip Mechanical properties of symmetric and asymmetric DNA A-tracts: implications for looping and nucleosome positioning
author_facet	Dršata, Tomáš Špačková, Naďa Jurečka, Petr Zgarbová, Marie Šponer, Jiří Lankaš, Filip
author_sort	Dršata, Tomáš
title	Mechanical properties of symmetric and asymmetric DNA A-tracts: implications for looping and nucleosome positioning
title_short	Mechanical properties of symmetric and asymmetric DNA A-tracts: implications for looping and nucleosome positioning
title_full	Mechanical properties of symmetric and asymmetric DNA A-tracts: implications for looping and nucleosome positioning
title_fullStr	Mechanical properties of symmetric and asymmetric DNA A-tracts: implications for looping and nucleosome positioning
title_full_unstemmed	Mechanical properties of symmetric and asymmetric DNA A-tracts: implications for looping and nucleosome positioning
title_sort	mechanical properties of symmetric and asymmetric dna a-tracts: implications for looping and nucleosome positioning
description	A-tracts are functionally important DNA sequences which induce helix bending and have peculiar structural properties. While A-tract structure has been qualitatively well characterized, their mechanical properties remain controversial. A-tracts appear structurally rigid and resist nucleosome formation, but seem flexible in DNA looping. In this work, we investigate mechanical properties of symmetric AnTn and asymmetric A2n tracts for n = 3, 4, 5 using two types of coarse-grained models. The first model represents DNA as an ensemble of interacting rigid bases with non-local quadratic deformation energy, the second one treats DNA as an anisotropically bendable and twistable elastic rod. Parameters for both models are inferred from microsecond long, atomic-resolution molecular dynamics simulations. We find that asymmetric A-tracts are more rigid than the control G/C-rich sequence in localized distortions relevant for nucleosome formation, but are more flexible in global bending and twisting relevant for looping. The symmetric tracts, in contrast, are more rigid than asymmetric tracts and the control, both locally and globally. Our results can reconcile the contradictory stiffness data on A-tracts and suggest symmetric A-tracts to be more efficient in nucleosome exclusion than the asymmetric ones. This would open a new possibility of gene expression manipulation using A-tracts.
publisher	Oxford University Press
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066768/
_version_	1612104737442758656

Mechanical properties of symmetric and asymmetric DNA A-tracts: implications for looping and nucleosome positioning

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