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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Federico Comoglio, Renato Paro
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a51adfc34e74418290baee6ef68c5a6d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a51adfc34e74418290baee6ef68c5a6d
record_format	dspace
spelling	oai:doaj.org-article:a51adfc34e74418290baee6ef68c5a6d2021-11-18T05:53:12ZCombinatorial modeling of chromatin features quantitatively predicts DNA replication timing in Drosophila.1553-734X1553-735810.1371/journal.pcbi.1003419https://doaj.org/article/a51adfc34e74418290baee6ef68c5a6d2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24465194/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358In 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.Federico ComoglioRenato ParoPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 10, Iss 1, p e1003419 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Federico Comoglio Renato Paro Combinatorial modeling of chromatin features quantitatively predicts DNA replication timing in Drosophila.
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	article
author	Federico Comoglio Renato Paro
author_facet	Federico Comoglio Renato Paro
author_sort	Federico Comoglio
title	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_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_sort	combinatorial modeling of chromatin features quantitatively predicts dna replication timing in drosophila.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/a51adfc34e74418290baee6ef68c5a6d
work_keys_str_mv	AT federicocomoglio combinatorialmodelingofchromatinfeaturesquantitativelypredictsdnareplicationtimingindrosophila AT renatoparo combinatorialmodelingofchromatinfeaturesquantitativelypredictsdnareplicationtimingindrosophila
_version_	1718424685182451712

Combinatorial modeling of chromatin features quantitatively predicts DNA replication timing in Drosophila.

Ejemplares similares