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Combinatorial Modeling of Chromatin Features Quantitatively Predicts DNA Replication Timing in Drosophila

In metazoans, each cell type follows a characteristic, spatio-temporally regulated DNA replication program. Histone modifications (HMs) and chromatin binding proteins (CBPs) are fundamental for a faithful progression and completion of this process. However, no individual HM is strictly indispensable...

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Autores principales: Comoglio, Federico, Paro, Renato
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900380/
https://www.ncbi.nlm.nih.gov/pubmed/24465194
http://dx.doi.org/10.1371/journal.pcbi.1003419
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author Comoglio, Federico
Paro, Renato
author_facet Comoglio, Federico
Paro, Renato
author_sort Comoglio, Federico
collection PubMed
description In metazoans, each cell type follows a characteristic, spatio-temporally regulated DNA replication program. Histone modifications (HMs) and chromatin binding proteins (CBPs) are fundamental for a faithful progression and completion of this process. However, no individual HM is strictly indispensable for origin function, suggesting that HMs may act combinatorially in analogy to the histone code hypothesis for transcriptional regulation. In contrast to gene expression however, the relationship between combinations of chromatin features and DNA replication timing has not yet been demonstrated. Here, by exploiting a comprehensive data collection consisting of 95 CBPs and HMs we investigated their combinatorial potential for the prediction of DNA replication timing in Drosophila using quantitative statistical models. We found that while combinations of CBPs exhibit moderate predictive power for replication timing, pairwise interactions between HMs lead to accurate predictions genome-wide that can be locally further improved by CBPs. Independent feature importance and model analyses led us to derive a simplified, biologically interpretable model of the relationship between chromatin landscape and replication timing reaching 80% of the full model accuracy using six model terms. Finally, we show that pairwise combinations of HMs are able to predict differential DNA replication timing across different cell types. All in all, our work provides support to the existence of combinatorial HM patterns for DNA replication and reveal cell-type independent key elements thereof, whose experimental investigation might contribute to elucidate the regulatory mode of this fundamental cellular process.
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spelling pubmed-39003802014-01-24 Combinatorial Modeling of Chromatin Features Quantitatively Predicts DNA Replication Timing in Drosophila Comoglio, Federico Paro, Renato PLoS Comput Biol Research Article In metazoans, each cell type follows a characteristic, spatio-temporally regulated DNA replication program. Histone modifications (HMs) and chromatin binding proteins (CBPs) are fundamental for a faithful progression and completion of this process. However, no individual HM is strictly indispensable for origin function, suggesting that HMs may act combinatorially in analogy to the histone code hypothesis for transcriptional regulation. In contrast to gene expression however, the relationship between combinations of chromatin features and DNA replication timing has not yet been demonstrated. Here, by exploiting a comprehensive data collection consisting of 95 CBPs and HMs we investigated their combinatorial potential for the prediction of DNA replication timing in Drosophila using quantitative statistical models. We found that while combinations of CBPs exhibit moderate predictive power for replication timing, pairwise interactions between HMs lead to accurate predictions genome-wide that can be locally further improved by CBPs. Independent feature importance and model analyses led us to derive a simplified, biologically interpretable model of the relationship between chromatin landscape and replication timing reaching 80% of the full model accuracy using six model terms. Finally, we show that pairwise combinations of HMs are able to predict differential DNA replication timing across different cell types. All in all, our work provides support to the existence of combinatorial HM patterns for DNA replication and reveal cell-type independent key elements thereof, whose experimental investigation might contribute to elucidate the regulatory mode of this fundamental cellular process. Public Library of Science 2014-01-23 /pmc/articles/PMC3900380/ /pubmed/24465194 http://dx.doi.org/10.1371/journal.pcbi.1003419 Text en http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Comoglio, Federico
Paro, Renato
Combinatorial Modeling of Chromatin Features Quantitatively Predicts DNA Replication Timing in Drosophila
title Combinatorial Modeling of Chromatin Features Quantitatively Predicts DNA Replication Timing in Drosophila
title_full Combinatorial Modeling of Chromatin Features Quantitatively Predicts DNA Replication Timing in Drosophila
title_fullStr Combinatorial Modeling of Chromatin Features Quantitatively Predicts DNA Replication Timing in Drosophila
title_full_unstemmed Combinatorial Modeling of Chromatin Features Quantitatively Predicts DNA Replication Timing in Drosophila
title_short Combinatorial Modeling of Chromatin Features Quantitatively Predicts DNA Replication Timing in Drosophila
title_sort combinatorial modeling of chromatin features quantitatively predicts dna replication timing in drosophila
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900380/
https://www.ncbi.nlm.nih.gov/pubmed/24465194
http://dx.doi.org/10.1371/journal.pcbi.1003419
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