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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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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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. |
format | Online Article Text |
id | pubmed-3900380 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT comogliofederico combinatorialmodelingofchromatinfeaturesquantitativelypredictsdnareplicationtimingindrosophila AT parorenato combinatorialmodelingofchromatinfeaturesquantitativelypredictsdnareplicationtimingindrosophila |