Integrative analysis of X-chromosome reactivation kinetics in a novel reprogramming system

The reactivation of the inactive X chromosome has the potential to provide a unique system to study the developmentally induced formation of euchromatin. However, insights into this process were hampered by the lack of adequate systems, which would allow the dissection of the process using high-thro...

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Detalles Bibliográficos
Autor: Bauer, Moritz
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/668761
Acceso en línea:http://hdl.handle.net/10803/668761
Access Level:acceso abierto
Palabra clave:Reprogramming
X-chromosome
Reactivation
Pluripotency
Chromatin
Reprogramación
Cromosoma X
Reactivación
Pluripotentia
Cromatina
575
id ES_e8c4618ffdbfda6ceace2240ff2b7abf
oai_identifier_str oai:www.tdx.cat:10803/668761
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Integrative analysis of X-chromosome reactivation kinetics in a novel reprogramming system
title Integrative analysis of X-chromosome reactivation kinetics in a novel reprogramming system
spellingShingle Integrative analysis of X-chromosome reactivation kinetics in a novel reprogramming system
Bauer, Moritz
Reprogramming
X-chromosome
Reactivation
Pluripotency
Chromatin
Reprogramación
Cromosoma X
Reactivación
Pluripotentia
Cromatina
575
title_short Integrative analysis of X-chromosome reactivation kinetics in a novel reprogramming system
title_full Integrative analysis of X-chromosome reactivation kinetics in a novel reprogramming system
title_fullStr Integrative analysis of X-chromosome reactivation kinetics in a novel reprogramming system
title_full_unstemmed Integrative analysis of X-chromosome reactivation kinetics in a novel reprogramming system
title_sort Integrative analysis of X-chromosome reactivation kinetics in a novel reprogramming system
dc.creator.none.fl_str_mv Bauer, Moritz
author Bauer, Moritz
author_facet Bauer, Moritz
author_role author
dc.contributor.none.fl_str_mv Payer, Bernhard
Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut
dc.subject.none.fl_str_mv Reprogramming
X-chromosome
Reactivation
Pluripotency
Chromatin
Reprogramación
Cromosoma X
Reactivación
Pluripotentia
Cromatina
575
topic Reprogramming
X-chromosome
Reactivation
Pluripotency
Chromatin
Reprogramación
Cromosoma X
Reactivación
Pluripotentia
Cromatina
575
description The reactivation of the inactive X chromosome has the potential to provide a unique system to study the developmentally induced formation of euchromatin. However, insights into this process were hampered by the lack of adequate systems, which would allow the dissection of the process using high-throughput sequencing techniques. Here I describe the development of a novel induced pluripotent stem cell reprogramming system that allows the isolation of cells poised for X-reactivation, subsequently achieving near-deterministic efficiency of X-reactivation. Utilizing this novel system, we were able to reveal that the reactivation of silenced genes occurs rapidly and can be divided into distinct initiation and completion phases. Similarly, we could show that chromatin opening of the inactive X proceeds in a two-step fashion, initiating in close proximity to previously open regions, and possibly being initiated by pluripotency factors. Finally, we could show that mega-domains and TADs correspond to two different levels of three-dimensional genome organization superimposed on the Xi, independent of gene expression. We conclude that gene expression and chromatin accessibility during X-reactivation share similar kinetics, while genome organization might follow distinct principles.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2021
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 http://hdl.handle.net/10803/668761
url http://hdl.handle.net/10803/668761
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 102 p.
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Universitat Pompeu Fabra
publisher.none.fl_str_mv Universitat Pompeu Fabra
dc.source.none.fl_str_mv TDX (Tesis Doctorals en Xarxa)
reponame:TDR. Tesis Doctorales en Red
instname:CBUC, CESCA
instname_str CBUC, CESCA
reponame_str TDR. Tesis Doctorales en Red
collection TDR. Tesis Doctorales en Red
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869422970198294528
spelling Integrative analysis of X-chromosome reactivation kinetics in a novel reprogramming systemBauer, MoritzReprogrammingX-chromosomeReactivationPluripotencyChromatinReprogramaciónCromosoma XReactivaciónPluripotentiaCromatina575The reactivation of the inactive X chromosome has the potential to provide a unique system to study the developmentally induced formation of euchromatin. However, insights into this process were hampered by the lack of adequate systems, which would allow the dissection of the process using high-throughput sequencing techniques. Here I describe the development of a novel induced pluripotent stem cell reprogramming system that allows the isolation of cells poised for X-reactivation, subsequently achieving near-deterministic efficiency of X-reactivation. Utilizing this novel system, we were able to reveal that the reactivation of silenced genes occurs rapidly and can be divided into distinct initiation and completion phases. Similarly, we could show that chromatin opening of the inactive X proceeds in a two-step fashion, initiating in close proximity to previously open regions, and possibly being initiated by pluripotency factors. Finally, we could show that mega-domains and TADs correspond to two different levels of three-dimensional genome organization superimposed on the Xi, independent of gene expression. We conclude that gene expression and chromatin accessibility during X-reactivation share similar kinetics, while genome organization might follow distinct principles.La reactivación del cromosoma X inactivo tiene el potencial de proporcionar un sistema único para estudiar la formación de eucromatina inducida por el desarrollo. Sin embargo, la comprensión de este proceso se vio obstaculizada por la falta de sistemas adecuados, lo que permitiría la disección del proceso utilizando técnicas de secuenciación de alto rendimiento. Aquí describo el desarrollo de un nuevo sistema de reprogramación de células madre pluripotentes inducidas que permite el aislamiento de células preparadas para la reactivación de X, logrando posteriormente la eficiencia casi determinista de la reactivación de X. Utilizando este novedoso sistema, pudimos revelar que la reactivación de genes silenciados ocurre rápidamente y puede dividirse en distintas fases de iniciación y finalización. Del mismo modo, podríamos mostrar que la apertura de cromatina de la X inactiva se realiza en dos pasos, iniciando en las proximidades de regiones previamente abiertas, y posiblemente iniciada por factores de pluripotencia. Finalmente, podríamos mostrar que los mega-domains y los TADs corresponden a dos niveles diferentes de organización del genoma tridimensional superpuestos en el Xi, independientemente de la expresión génica. Llegamos a la conclusión de que la expresión génica y la accesibilidad a la cromatina durante la reactivación X comparten una cinética similar, mientras que la organización del genoma podría seguir principios distintos.Programa de doctorat en BiomedicinaUniversitat Pompeu FabraPayer, BernhardUniversitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut202020212020info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersion102 p.application/pdfapplication/pdfhttp://hdl.handle.net/10803/668761TDX (Tesis Doctorals en Xarxa)reponame:TDR. Tesis Doctorales en Redinstname:CBUC, CESCAInglésADVERTIMENT. Tots els drets reservats. L'accés als continguts d'aquesta tesi doctoral i la seva utilització ha de respectar els drets de la persona autora. Pot ser utilitzada per a consulta o estudi personal, així com en activitats o materials d'investigació i docència en els termes establerts a l'art. 32 del Text Refós de la Llei de Propietat Intel·lectual (RDL 1/1996). Per altres utilitzacions es requereix l'autorització prèvia i expressa de la persona autora. En qualsevol cas, en la utilització dels seus continguts caldrà indicar de forma clara el nom i cognoms de la persona autora i el títol de la tesi doctoral. No s'autoritza la seva reproducció o altres formes d'explotació efectuades amb finalitats de lucre ni la seva comunicació pública des d'un lloc aliè al servei TDX. Tampoc s'autoritza la presentació del seu contingut en una finestra o marc aliè a TDX (framing). Aquesta reserva de drets afecta tant als continguts de la tesi com als seus resums i índexs.info:eu-repo/semantics/openAccessoai:www.tdx.cat:10803/6687612026-06-14T12:46:07Z
score 15,300719

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