Differential contribution to gene expression prediction of histone modifications at enhancers or promoters.

The ChIP-seq signal of histone modifications at promoters is a good predictor of gene expression in different cellular contexts, but whether this is also true at enhancers is not clear. To address this issue, we develop quantitative models to characterize the relationship of gene expression with his...

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Autores principales:	Mar González-Ramírez, Cecilia Ballaré, Francesca Mugianesi, Malte Beringer, Alexandra Santanach, Enrique Blanco, Luciano Di Croce
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/415ee9a20d154851a028a154237d912c
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spelling	oai:doaj.org-article:415ee9a20d154851a028a154237d912c2021-12-02T19:57:52ZDifferential contribution to gene expression prediction of histone modifications at enhancers or promoters.1553-734X1553-735810.1371/journal.pcbi.1009368https://doaj.org/article/415ee9a20d154851a028a154237d912c2021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009368https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The ChIP-seq signal of histone modifications at promoters is a good predictor of gene expression in different cellular contexts, but whether this is also true at enhancers is not clear. To address this issue, we develop quantitative models to characterize the relationship of gene expression with histone modifications at enhancers or promoters. We use embryonic stem cells (ESCs), which contain a full spectrum of active and repressed (poised) enhancers, to train predictive models. As many poised enhancers in ESCs switch towards an active state during differentiation, predictive models can also be trained on poised enhancers throughout differentiation and in development. Remarkably, we determine that histone modifications at enhancers, as well as promoters, are predictive of gene expression in ESCs and throughout differentiation and development. Importantly, we demonstrate that their contribution to the predictive models varies depending on their location in enhancers or promoters. Moreover, we use a local regression (LOESS) to normalize sequencing data from different sources, which allows us to apply predictive models trained in a specific cellular context to a different one. We conclude that the relationship between gene expression and histone modifications at enhancers is universal and different from promoters. Our study provides new insight into how histone modifications relate to gene expression based on their location in enhancers or promoters.Mar González-RamírezCecilia BallaréFrancesca MugianesiMalte BeringerAlexandra SantanachEnrique BlancoLuciano Di CrocePublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 9, p e1009368 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Mar González-Ramírez Cecilia Ballaré Francesca Mugianesi Malte Beringer Alexandra Santanach Enrique Blanco Luciano Di Croce Differential contribution to gene expression prediction of histone modifications at enhancers or promoters.
description	The ChIP-seq signal of histone modifications at promoters is a good predictor of gene expression in different cellular contexts, but whether this is also true at enhancers is not clear. To address this issue, we develop quantitative models to characterize the relationship of gene expression with histone modifications at enhancers or promoters. We use embryonic stem cells (ESCs), which contain a full spectrum of active and repressed (poised) enhancers, to train predictive models. As many poised enhancers in ESCs switch towards an active state during differentiation, predictive models can also be trained on poised enhancers throughout differentiation and in development. Remarkably, we determine that histone modifications at enhancers, as well as promoters, are predictive of gene expression in ESCs and throughout differentiation and development. Importantly, we demonstrate that their contribution to the predictive models varies depending on their location in enhancers or promoters. Moreover, we use a local regression (LOESS) to normalize sequencing data from different sources, which allows us to apply predictive models trained in a specific cellular context to a different one. We conclude that the relationship between gene expression and histone modifications at enhancers is universal and different from promoters. Our study provides new insight into how histone modifications relate to gene expression based on their location in enhancers or promoters.
format	article
author	Mar González-Ramírez Cecilia Ballaré Francesca Mugianesi Malte Beringer Alexandra Santanach Enrique Blanco Luciano Di Croce
author_facet	Mar González-Ramírez Cecilia Ballaré Francesca Mugianesi Malte Beringer Alexandra Santanach Enrique Blanco Luciano Di Croce
author_sort	Mar González-Ramírez
title	Differential contribution to gene expression prediction of histone modifications at enhancers or promoters.
title_short	Differential contribution to gene expression prediction of histone modifications at enhancers or promoters.
title_full	Differential contribution to gene expression prediction of histone modifications at enhancers or promoters.
title_fullStr	Differential contribution to gene expression prediction of histone modifications at enhancers or promoters.
title_full_unstemmed	Differential contribution to gene expression prediction of histone modifications at enhancers or promoters.
title_sort	differential contribution to gene expression prediction of histone modifications at enhancers or promoters.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/415ee9a20d154851a028a154237d912c
work_keys_str_mv	AT margonzalezramirez differentialcontributiontogeneexpressionpredictionofhistonemodificationsatenhancersorpromoters AT ceciliaballare differentialcontributiontogeneexpressionpredictionofhistonemodificationsatenhancersorpromoters AT francescamugianesi differentialcontributiontogeneexpressionpredictionofhistonemodificationsatenhancersorpromoters AT malteberinger differentialcontributiontogeneexpressionpredictionofhistonemodificationsatenhancersorpromoters AT alexandrasantanach differentialcontributiontogeneexpressionpredictionofhistonemodificationsatenhancersorpromoters AT enriqueblanco differentialcontributiontogeneexpressionpredictionofhistonemodificationsatenhancersorpromoters AT lucianodicroce differentialcontributiontogeneexpressionpredictionofhistonemodificationsatenhancersorpromoters
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Differential contribution to gene expression prediction of histone modifications at enhancers or promoters.

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