Epigenetic information contained in male germ cell chromatin-associated proteins and its potential impact on the reproductive function

[eng] Contrasting the traditional idea of the male gamete being a simple carrier of the paternal DNA, evidence in the last decades revealed that the sperm cell provides the embryo with different layers of epigenetic information, which is not limited to DNA methylation and non-coding RNAs but also in...

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Autor: Iglesia Rodríguez, Alberto de la
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/208863
Acceso en línea:https://hdl.handle.net/2445/208863
http://hdl.handle.net/10803/690344
Access Level:acceso abierto
Palabra clave:Epigenètica
Cromatina
Espermatozoides
Epigenetics
Chromatin
Spermatozoa
id ES_e0fbb9ea06aaf8aa50da45ea43a17fa3
oai_identifier_str oai:diposit.ub.edu:2445/208863
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Epigenetic information contained in male germ cell chromatin-associated proteins and its potential impact on the reproductive function
title Epigenetic information contained in male germ cell chromatin-associated proteins and its potential impact on the reproductive function
spellingShingle Epigenetic information contained in male germ cell chromatin-associated proteins and its potential impact on the reproductive function
Iglesia Rodríguez, Alberto de la
Epigenètica
Cromatina
Espermatozoides
Epigenetics
Chromatin
Spermatozoa
title_short Epigenetic information contained in male germ cell chromatin-associated proteins and its potential impact on the reproductive function
title_full Epigenetic information contained in male germ cell chromatin-associated proteins and its potential impact on the reproductive function
title_fullStr Epigenetic information contained in male germ cell chromatin-associated proteins and its potential impact on the reproductive function
title_full_unstemmed Epigenetic information contained in male germ cell chromatin-associated proteins and its potential impact on the reproductive function
title_sort Epigenetic information contained in male germ cell chromatin-associated proteins and its potential impact on the reproductive function
dc.creator.none.fl_str_mv Iglesia Rodríguez, Alberto de la
author Iglesia Rodríguez, Alberto de la
author_facet Iglesia Rodríguez, Alberto de la
author_role author
dc.contributor.none.fl_str_mv Oliva Virgili, Rafael
Castillo Corullón, Judit
Universitat de Barcelona. Facultat de Medicina i Ciències de la Salut
dc.subject.none.fl_str_mv Epigenètica
Cromatina
Espermatozoides
Epigenetics
Chromatin
Spermatozoa
topic Epigenètica
Cromatina
Espermatozoides
Epigenetics
Chromatin
Spermatozoa
description [eng] Contrasting the traditional idea of the male gamete being a simple carrier of the paternal DNA, evidence in the last decades revealed that the sperm cell provides the embryo with different layers of epigenetic information, which is not limited to DNA methylation and non-coding RNAs but also involves the protein fraction of the sperm chromatin. Posttranslational modifications (PTMs) of chromatin-associated proteins, together with a complex population of proteins with gene regulatory roles, would also have an impact in fertilization and pre-implantation embryo development. Furthermore, the sperm chromatin, understood as the association between DNA and two different types of proteins, histones and protamines, both bearing PTMs, and resulting in two distinct genome compaction states, arises as a new concept of epigenetic mark that is exclusive for the male gamete. The relevance and peculiarities of sperm chromatin have attracted interest over the years, and many efforts have been made to disentangle it, not only in mature sperm but also during spermatid differentiation. However, male germ cells’ chromatin is as attractive as challenging, and its study requires the adaptation of conventional techniques or application of new ones. Despite that, many important factors have been related with the regulation and formation of the sperm chromatin, as well as with the correct transmission of parental epigenetic information to the zygote. Thus, protamines, histones, and their PTMs, both during male gamete development and once matured, as well as the peculiarly compacted chromatin structure of mature sperm, emerge as interesting features to be further studied to increase the current knowledge on the epigenetic content of the protein fraction of sperm chromatin and its potential involvement in cases of unexplained male infertility. The objectives of this doctoral thesis are: 1) To explore histone PTMs involved in the process of nucleo-histone to nucleo-protamine transition and their epigenetic potential, 2) To increase the knowledge on protamine proteoforms, with a special focus on protamine phosphorylation, and 3) To apply innovative approaches to the study of the sperm chromatin and chromatin compaction defects through the use of small X-ray scattering (SAXS) with synchrotron light for the nanoscale characterization of the sperm nucleus. Besides, objective 1 is subdivided into 1a) to describe alterations of a global histone H4 acetylation pattern during the spermatogenesis in different testicular affections, and 1b) to characterize specific novel acylations during spermatogenesis and in mature sperm (H4K5 acetylation and butyrylation) and their relationship with sperm quality. In turn, objective 2 comprises 2a) to define the normal profile of protamine PTMs through top-down proteomics and to identify alterations in the protamine proteoforms related with unexplained infertility and 2b) to explore the protein interactive networks of proteins modulating protamine phosphorylation.
publishDate 2022
dc.date.none.fl_str_mv 2022
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/2445/208863
http://hdl.handle.net/10803/690344
url https://hdl.handle.net/2445/208863
http://hdl.handle.net/10803/690344
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv (c) Iglesia Rodríguez, Alberto de la, 2024
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Iglesia Rodríguez, Alberto de la, 2024
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 - Medicina i Ciències de la Salut
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_ 1869422252004474880
spelling Epigenetic information contained in male germ cell chromatin-associated proteins and its potential impact on the reproductive functionIglesia Rodríguez, Alberto de laEpigenèticaCromatinaEspermatozoidesEpigeneticsChromatinSpermatozoa[eng] Contrasting the traditional idea of the male gamete being a simple carrier of the paternal DNA, evidence in the last decades revealed that the sperm cell provides the embryo with different layers of epigenetic information, which is not limited to DNA methylation and non-coding RNAs but also involves the protein fraction of the sperm chromatin. Posttranslational modifications (PTMs) of chromatin-associated proteins, together with a complex population of proteins with gene regulatory roles, would also have an impact in fertilization and pre-implantation embryo development. Furthermore, the sperm chromatin, understood as the association between DNA and two different types of proteins, histones and protamines, both bearing PTMs, and resulting in two distinct genome compaction states, arises as a new concept of epigenetic mark that is exclusive for the male gamete. The relevance and peculiarities of sperm chromatin have attracted interest over the years, and many efforts have been made to disentangle it, not only in mature sperm but also during spermatid differentiation. However, male germ cells’ chromatin is as attractive as challenging, and its study requires the adaptation of conventional techniques or application of new ones. Despite that, many important factors have been related with the regulation and formation of the sperm chromatin, as well as with the correct transmission of parental epigenetic information to the zygote. Thus, protamines, histones, and their PTMs, both during male gamete development and once matured, as well as the peculiarly compacted chromatin structure of mature sperm, emerge as interesting features to be further studied to increase the current knowledge on the epigenetic content of the protein fraction of sperm chromatin and its potential involvement in cases of unexplained male infertility. The objectives of this doctoral thesis are: 1) To explore histone PTMs involved in the process of nucleo-histone to nucleo-protamine transition and their epigenetic potential, 2) To increase the knowledge on protamine proteoforms, with a special focus on protamine phosphorylation, and 3) To apply innovative approaches to the study of the sperm chromatin and chromatin compaction defects through the use of small X-ray scattering (SAXS) with synchrotron light for the nanoscale characterization of the sperm nucleus. Besides, objective 1 is subdivided into 1a) to describe alterations of a global histone H4 acetylation pattern during the spermatogenesis in different testicular affections, and 1b) to characterize specific novel acylations during spermatogenesis and in mature sperm (H4K5 acetylation and butyrylation) and their relationship with sperm quality. In turn, objective 2 comprises 2a) to define the normal profile of protamine PTMs through top-down proteomics and to identify alterations in the protamine proteoforms related with unexplained infertility and 2b) to explore the protein interactive networks of proteins modulating protamine phosphorylation.[spa] Contrariamente a la idea tradicional de que el gameto masculino era un simple portador del ADN paterno, los avances científicos de las últimas décadas han revelado que el espermatozoide aporta diferentes niveles de información epigenética al embrión. Así, las modificaciones postraduccionales (MPTs) de proteínas asociadas al DNA y la distribución diferencial del genoma paterno a lo largo de la cromatina, junto a una compleja población de ARNs no codificantes y proteínas con funciones de regulación génica, tendrían un impacto no solo en la fecundación si no también en el desarrollo embrionario preimplantacional. La cromatina espermática está formada principalmente por la asociación entre el ADN y dos tipos de proteínas diferentes, histonas y protaminas, que contienen MPTs específicas y presentan distintos estados de compactación del genoma, lo que da lugar a un nuevo concepto de marca epigenética exclusivo para esta célula. La relevancia y peculiaridades de la cromatina del gameto masculino han atraído interés a lo largo de los años, y se han realizado muchos esfuerzos para desentrañar todo lo que la confiere, no solo a nivel de espermatozoide maduro sino también durante la diferenciación de las espermátidas en la última fase de la espermatogénesis. Sin embargo, la cromatina de las células germinales masculinas es tan atractiva como compleja, requiriendo la adaptación de técnicas convencionales y la aplicación de otras nuevas para su estudio. A pesar de ello, se han conseguido identificar muchos factores importantes en la regulación y formación de la cromatina espermática, así como en la correcta transmisión de la información epigenética paterna al zigoto. Así, las MPTs de protaminas e histonas, tanto durante el desarrollo del gameto masculino como ya una vez madurados, y la estructura resultante tras la compactación de la cromatina espermática, surgen como rasgos interesantes a estudiar en mayor profundidad para descifrar su implicación en los casos de infertilidad masculina de origen desconocido. La tesis doctoral tiene tres objetivos principales: 1) explorar MPTs de histonas involucradas en el proceso de transición de nucleo-histona a nucleo-protamina y su potencial epigenético, 2) Aumentar el conocimiento actual sobre las proteoformas de las protaminas, con especial atención en la fosforilación de las protaminas, y 3) Aplicar estrategias innovadoras al estudio de la cromatina espermática y errores de compactación, mediante el uso de dispersión de rayos X de ángulo pequeño (SAXS) con luz de sincrotrón para la caracterización del núcleo espermático a nivel de nanoescala. A su vez, el objetivo 1 se subdivide en 1a) describir alteraciones del patrón que sigue la acetilación global de la histona H4 durante la espermatogénesis en diferentes patologías testiculares, y 1b) caracterizar acilaciones específicas (acetilación y butirilación en H4K5) durante la espermatogénesis y en espermatozoide maduro, así como su relación con la calidad espermática. El objetivo 2 comprende 2a) definir el perfil normal de proteoformas de las protaminas mediante proteómica top-down e identificar alteraciones en las proteoformas de las protaminas en relación con infertilidad de origen desconocido, y 2b) explorar la red proteica interactiva de proteínas que modulan la fosforilación de las protaminasUniversitat de BarcelonaOliva Virgili, RafaelCastillo Corullón, JuditUniversitat de Barcelona. Facultat de Medicina i Ciències de la Salut2022info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/208863http://hdl.handle.net/10803/690344Tesis Doctorals - Facultat - Medicina i Ciències de la Salutreponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglés(c) Iglesia Rodríguez, Alberto de la, 2024info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2088632026-05-27T06:46:51Z
score 15,300719

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