Thermodynamic modeling of genome-wide nucleosome depleted regions in yeast.

Nucleosome positioning in the genome is essential for the regulation of many nuclear processes. We currently have limited capability to predict nucleosome positioning in vivo, especially the locations and sizes of nucleosome depleted regions (NDRs). Here, we present a thermodynamic model that incorp...

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Main Authors: Hungyo Kharerin, Lu Bai
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-01-01
Series:PLoS Computational Biology
Online Access:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008560&type=printable
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author Hungyo Kharerin
Lu Bai
author_facet Hungyo Kharerin
Lu Bai
author_sort Hungyo Kharerin
collection DOAJ
description Nucleosome positioning in the genome is essential for the regulation of many nuclear processes. We currently have limited capability to predict nucleosome positioning in vivo, especially the locations and sizes of nucleosome depleted regions (NDRs). Here, we present a thermodynamic model that incorporates the intrinsic affinity of histones, competitive binding of sequence-specific factors, and nucleosome remodeling to predict nucleosome positioning in budding yeast. The model shows that the intrinsic affinity of histones, at near-saturating histone concentration, is not sufficient in generating NDRs in the genome. However, the binding of a few factors, especially RSC towards GC-rich and poly(A/T) sequences, allows us to predict ~ 66% of genome-wide NDRs. The model also shows that nucleosome remodeling activity is required to predict the correct NDR sizes. The validity of the model was further supported by the agreement between the predicted and the measured nucleosome positioning upon factor deletion or on exogenous sequences introduced into yeast. Overall, our model quantitatively evaluated the impact of different genetic components on NDR formation and illustrated the vital roles of sequence-specific factors and nucleosome remodeling in this process.
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spelling doaj-art-e8f55529578e481dbc14ed2b73d0e9e42025-08-20T02:17:05ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582021-01-01171e100856010.1371/journal.pcbi.1008560Thermodynamic modeling of genome-wide nucleosome depleted regions in yeast.Hungyo KharerinLu BaiNucleosome positioning in the genome is essential for the regulation of many nuclear processes. We currently have limited capability to predict nucleosome positioning in vivo, especially the locations and sizes of nucleosome depleted regions (NDRs). Here, we present a thermodynamic model that incorporates the intrinsic affinity of histones, competitive binding of sequence-specific factors, and nucleosome remodeling to predict nucleosome positioning in budding yeast. The model shows that the intrinsic affinity of histones, at near-saturating histone concentration, is not sufficient in generating NDRs in the genome. However, the binding of a few factors, especially RSC towards GC-rich and poly(A/T) sequences, allows us to predict ~ 66% of genome-wide NDRs. The model also shows that nucleosome remodeling activity is required to predict the correct NDR sizes. The validity of the model was further supported by the agreement between the predicted and the measured nucleosome positioning upon factor deletion or on exogenous sequences introduced into yeast. Overall, our model quantitatively evaluated the impact of different genetic components on NDR formation and illustrated the vital roles of sequence-specific factors and nucleosome remodeling in this process.https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008560&type=printable
spellingShingle Hungyo Kharerin
Lu Bai
Thermodynamic modeling of genome-wide nucleosome depleted regions in yeast.
PLoS Computational Biology
title Thermodynamic modeling of genome-wide nucleosome depleted regions in yeast.
title_full Thermodynamic modeling of genome-wide nucleosome depleted regions in yeast.
title_fullStr Thermodynamic modeling of genome-wide nucleosome depleted regions in yeast.
title_full_unstemmed Thermodynamic modeling of genome-wide nucleosome depleted regions in yeast.
title_short Thermodynamic modeling of genome-wide nucleosome depleted regions in yeast.
title_sort thermodynamic modeling of genome wide nucleosome depleted regions in yeast
url https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008560&type=printable
work_keys_str_mv AT hungyokharerin thermodynamicmodelingofgenomewidenucleosomedepletedregionsinyeast
AT lubai thermodynamicmodelingofgenomewidenucleosomedepletedregionsinyeast