Molecular mechanisms for active DNA demethylation in cellular immune models

[eng] Secondly, we also explored the role of DNA demethylation in the regulation of immunosuppressive phenotype of monocyte- (MO) derived dendritic cells (DC) differentiated in presence of vitamin D, focusing on the interplay among different signal-dependent transcription factors (TF) and the DNA de...

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Detalles Bibliográficos
Autor: Català Moll, Francisco
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/180962
Acceso en línea:https://hdl.handle.net/2445/180962
http://hdl.handle.net/10803/672707
Access Level:acceso abierto
Palabra clave:Epigenètica
Immunologia
Genòmica
Metilació
ADN
Biocompatibilitat
Epigenetics
Immunology
Genomics
Methylation
DNA
Biocompatibility
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oai_identifier_str oai:diposit.ub.edu:2445/180962
network_acronym_str ES
network_name_str España
repository_id_str
spelling Molecular mechanisms for active DNA demethylation in cellular immune modelsCatalà Moll, FranciscoEpigenèticaImmunologiaGenòmicaMetilacióADNBiocompatibilitatEpigeneticsImmunologyGenomicsMethylationDNABiocompatibility[eng] Secondly, we also explored the role of DNA demethylation in the regulation of immunosuppressive phenotype of monocyte- (MO) derived dendritic cells (DC) differentiated in presence of vitamin D, focusing on the interplay among different signal-dependent transcription factors (TF) and the DNA demethylation machinery. In this study, we performed high-throughput DNA methylation screening of both inflammatory DCs and DCs differentiated in presence of vitamin D (TL). DNA methylation analysis revealed extensive condition-specific DNA demethylation events associated with differential immune properties. As expected, we observed that demethylation occurs in enhancer regions and displays an inverse correlation with gene expression. We proved that, vitamin D receptor (VDR) can bind to closed chromatin and correlates with TL-specific demethylation. Interestingly, we observed that tolerogenic properties in DCs are acquired together with activation of the IL- 6/JAK/STAT3 pathway. In fact, VDR directly binds the IL-6 gene and JAK2- mediated STAT3 phosphorylation is specific to vitamin D-stimulation. In addition, we also observed that VDR interacts with both STAT3 and TET2. Finally, we reported that pharmacological inhibition of STAT3 phosphorylation reverts the vitamin–induced tolerogenic properties of DCs.Universitat de BarcelonaBallestar Tarín, EstebanRodríguez Ubreva, JavierUniversitat de Barcelona. Facultat de Biologia2020info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/180962http://hdl.handle.net/10803/672707Tesis Doctorals - Facultat - Biologiareponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglés(c) Català Moll, Francisco, 2021info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1809622026-05-27T06:46:51Z
dc.title.none.fl_str_mv Molecular mechanisms for active DNA demethylation in cellular immune models
title Molecular mechanisms for active DNA demethylation in cellular immune models
spellingShingle Molecular mechanisms for active DNA demethylation in cellular immune models
Català Moll, Francisco
Epigenètica
Immunologia
Genòmica
Metilació
ADN
Biocompatibilitat
Epigenetics
Immunology
Genomics
Methylation
DNA
Biocompatibility
title_short Molecular mechanisms for active DNA demethylation in cellular immune models
title_full Molecular mechanisms for active DNA demethylation in cellular immune models
title_fullStr Molecular mechanisms for active DNA demethylation in cellular immune models
title_full_unstemmed Molecular mechanisms for active DNA demethylation in cellular immune models
title_sort Molecular mechanisms for active DNA demethylation in cellular immune models
dc.creator.none.fl_str_mv Català Moll, Francisco
author Català Moll, Francisco
author_facet Català Moll, Francisco
author_role author
dc.contributor.none.fl_str_mv Ballestar Tarín, Esteban
Rodríguez Ubreva, Javier
Universitat de Barcelona. Facultat de Biologia
dc.subject.none.fl_str_mv Epigenètica
Immunologia
Genòmica
Metilació
ADN
Biocompatibilitat
Epigenetics
Immunology
Genomics
Methylation
DNA
Biocompatibility
topic Epigenètica
Immunologia
Genòmica
Metilació
ADN
Biocompatibilitat
Epigenetics
Immunology
Genomics
Methylation
DNA
Biocompatibility
description [eng] Secondly, we also explored the role of DNA demethylation in the regulation of immunosuppressive phenotype of monocyte- (MO) derived dendritic cells (DC) differentiated in presence of vitamin D, focusing on the interplay among different signal-dependent transcription factors (TF) and the DNA demethylation machinery. In this study, we performed high-throughput DNA methylation screening of both inflammatory DCs and DCs differentiated in presence of vitamin D (TL). DNA methylation analysis revealed extensive condition-specific DNA demethylation events associated with differential immune properties. As expected, we observed that demethylation occurs in enhancer regions and displays an inverse correlation with gene expression. We proved that, vitamin D receptor (VDR) can bind to closed chromatin and correlates with TL-specific demethylation. Interestingly, we observed that tolerogenic properties in DCs are acquired together with activation of the IL- 6/JAK/STAT3 pathway. In fact, VDR directly binds the IL-6 gene and JAK2- mediated STAT3 phosphorylation is specific to vitamin D-stimulation. In addition, we also observed that VDR interacts with both STAT3 and TET2. Finally, we reported that pharmacological inhibition of STAT3 phosphorylation reverts the vitamin–induced tolerogenic properties of DCs.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/180962
http://hdl.handle.net/10803/672707
url https://hdl.handle.net/2445/180962
http://hdl.handle.net/10803/672707
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv (c) Català Moll, Francisco, 2021
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Català Moll, Francisco, 2021
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universitat de Barcelona
publisher.none.fl_str_mv Universitat de Barcelona
dc.source.none.fl_str_mv Tesis Doctorals - Facultat - Biologia
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869415936592707584
score 15,301603

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