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

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• dc.contributor.author González Ramírez, Mar, 1991-
• dc.contributor.author Ballaré, Cecilia Julia
• dc.contributor.author Mugianesi, Francesca
• dc.contributor.author Beringer, Malte
• dc.contributor.author Santanach Buxaderas, Alexandra, 1988-
• dc.contributor.author Blanco, Enrique
• dc.contributor.author Di Croce, Luciano
• dc.date.accessioned 2021-12-14T11:07:15Z
• dc.date.available 2021-12-14T11:07:15Z
• dc.date.issued 2021
• dc.description.abstract 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.
• dc.description.sponsorship The work in the Di Croce laboratory is supported by grants from the Spanish Ministry of Science and Innovation (BFU2016-75008-P, and PID2019-108322GB-100), “Fundación Vencer El Cancer” (VEC), the European Regional Development Fund (FEDER), and from AGAUR (SGR 2017-2019, AGAUR 2019 FI_B 00426). We acknowledge support from the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa and the CERCA Programme/Generalitat de Catalunya
• dc.format.mimetype application/pdf
• dc.identifier.citation González-Ramírez M, Ballaré C, Mugianesi F, Beringer M, Santanach A, Blanco E et al. Differential contribution to gene expression prediction of histone modifications at enhancers or promoters. PLoS Comput Biol. 2021 Sep 2;17(9):e1009368. DOI: 10.1371/journal.pcbi.1009368
• dc.identifier.doi http://dx.doi.org/10.1371/journal.pcbi.1009368
• dc.identifier.issn 1553-734X
• dc.identifier.uri http://hdl.handle.net/10230/49198
• dc.language.iso eng
• dc.publisher Public Library of Science (PLoS)
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2016-75008-P
• dc.rights © 2021 González-Ramírez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.other Genètica
• dc.subject.other Histones
• dc.title Differential contribution to gene expression prediction of histone modifications at enhancers or promoters
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion