Systematic characterization of the genome-wide and nuclear distribution of six linker histone H1 variants in human cancer cells

[eng] The histone H1 family comprises up to seven members in human somatic cells. However, H1 studies have been limited by the lack of specific ChIP-grade antibodies. Here, we have mapped six endogenous H1 variants in T47D breast cancer cells, which represent the whole somatic H1 complement in this...

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Autor: Salinas Pena, Mónica
Tipo de documento: tese
Estado:Versão publicada
Data de publicação:2023
País:España
Recursos:Universidad de Barcelona
Repositório:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/202890
Acesso em linha:https://hdl.handle.net/2445/202890
http://hdl.handle.net/10803/689137
Access Level:Acceso aberto
Palavra-chave:Epigenètica
Cromatina
Histones
Seqüència d'aminoàcids
Oncologia
Epigenetics
Chromatin
Amino acid sequence
Oncology
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spelling Systematic characterization of the genome-wide and nuclear distribution of six linker histone H1 variants in human cancer cellsSalinas Pena, MónicaEpigenèticaCromatinaHistonesSeqüència d'aminoàcidsOncologiaEpigeneticsChromatinAmino acid sequenceOncology[eng] The histone H1 family comprises up to seven members in human somatic cells. However, H1 studies have been limited by the lack of specific ChIP-grade antibodies. Here, we have mapped six endogenous H1 variants in T47D breast cancer cells, which represent the whole somatic H1 complement in this cell line. ChIP-Seq experiments indicate that H1 variants are categorized into two large groups depending on the local GC content: H1.0, H1.2, H1.3 and H1.5 are enriched at low-GC regions while H1.4 and H1X are more abundant at high-GC genomic regions. Data also uncovers common features for H1 variants, highlighting the existing balance between redundancy and specificity. Examination of H1 variants abundance within repetitive elements classes denoted that H1.0, H1.2, H1.3 and H1.5 are enriched within Satellite, LINE, LTR or DNA classes while H1.4 and H1X are enriched within SINE or ‘Other’ classes. This last category comprises SVA retrotransposons, which emerged along hominoid evolution. Interestingly, we have determined that H1X abundance gradually increases from older SVA_A to humanrestricted SVA_F families. This unprecedented association of H1 variants abundance and transposable elements (TEs) evolutionary age is also observed across different TE classes. Both H1X and H1.4 are enriched within the most recently evolved TEs along primate evolution, including not only SVAs but also younger Alu, LINE-L1 or LTR repeats. Conversely, H1.2, H1.3, H1.5, H1.0 are enriched in older TEs. Confocal and super-resolution microscopy experiments further confirm the differential distribution of H1 variants and their distinct contribution to chromatin structure. H1.2, H1.3 and H1.5 are enriched towards the nuclear periphery or lamina-associated domains. H1.4 and H1X show a punctuated pattern throughout the nucleus, with H1X being particularly enriched at nucleoli. H1.0 forms enrichment territories that tend to be peripheral. Moreover, depletion of H1.2, either alone or in combination with H1.4, leads to a general chromatin decompaction that is not observed upon single H1.4 or H1X depletion. Extensive analysis of multiple cell lines revealed the existence of certain universal distribution features despite variations in the H1 somatic repertoire. Specifically, H1.2, H1.3 and H1.5 consistently show enrichments towards the nuclear periphery in all cell lines examined, suggesting their universal role as components of lamina-associated domains. H1X, whose nucleolar presence is evident in all cell lines, is enriched at high- GC regions and younger SVA and Alu elements, as observed in T47D cells. In conclusion, we provide the first systematic comparison of six endogenous H1 variants within a mammalian cell type, while also addressing their differential distribution among multiple cell lines. Altogether, our results support H1 variants heterogeneity and highlight their significance as key organizers and regulators of chromatin.Universitat de BarcelonaJordan Vallès, AlbertUniversitat de Barcelona. Facultat de Biologia2023info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/202890http://hdl.handle.net/10803/689137Tesis Doctorals - Facultat - Biologiareponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaIngléscc by-nc-nd (c) Salinas Pena, Mónica, 2023http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2028902026-05-27T06:46:51Z
dc.title.none.fl_str_mv Systematic characterization of the genome-wide and nuclear distribution of six linker histone H1 variants in human cancer cells
title Systematic characterization of the genome-wide and nuclear distribution of six linker histone H1 variants in human cancer cells
spellingShingle Systematic characterization of the genome-wide and nuclear distribution of six linker histone H1 variants in human cancer cells
Salinas Pena, Mónica
Epigenètica
Cromatina
Histones
Seqüència d'aminoàcids
Oncologia
Epigenetics
Chromatin
Amino acid sequence
Oncology
title_short Systematic characterization of the genome-wide and nuclear distribution of six linker histone H1 variants in human cancer cells
title_full Systematic characterization of the genome-wide and nuclear distribution of six linker histone H1 variants in human cancer cells
title_fullStr Systematic characterization of the genome-wide and nuclear distribution of six linker histone H1 variants in human cancer cells
title_full_unstemmed Systematic characterization of the genome-wide and nuclear distribution of six linker histone H1 variants in human cancer cells
title_sort Systematic characterization of the genome-wide and nuclear distribution of six linker histone H1 variants in human cancer cells
dc.creator.none.fl_str_mv Salinas Pena, Mónica
author Salinas Pena, Mónica
author_facet Salinas Pena, Mónica
author_role author
dc.contributor.none.fl_str_mv Jordan Vallès, Albert
Universitat de Barcelona. Facultat de Biologia
dc.subject.none.fl_str_mv Epigenètica
Cromatina
Histones
Seqüència d'aminoàcids
Oncologia
Epigenetics
Chromatin
Amino acid sequence
Oncology
topic Epigenètica
Cromatina
Histones
Seqüència d'aminoàcids
Oncologia
Epigenetics
Chromatin
Amino acid sequence
Oncology
description [eng] The histone H1 family comprises up to seven members in human somatic cells. However, H1 studies have been limited by the lack of specific ChIP-grade antibodies. Here, we have mapped six endogenous H1 variants in T47D breast cancer cells, which represent the whole somatic H1 complement in this cell line. ChIP-Seq experiments indicate that H1 variants are categorized into two large groups depending on the local GC content: H1.0, H1.2, H1.3 and H1.5 are enriched at low-GC regions while H1.4 and H1X are more abundant at high-GC genomic regions. Data also uncovers common features for H1 variants, highlighting the existing balance between redundancy and specificity. Examination of H1 variants abundance within repetitive elements classes denoted that H1.0, H1.2, H1.3 and H1.5 are enriched within Satellite, LINE, LTR or DNA classes while H1.4 and H1X are enriched within SINE or ‘Other’ classes. This last category comprises SVA retrotransposons, which emerged along hominoid evolution. Interestingly, we have determined that H1X abundance gradually increases from older SVA_A to humanrestricted SVA_F families. This unprecedented association of H1 variants abundance and transposable elements (TEs) evolutionary age is also observed across different TE classes. Both H1X and H1.4 are enriched within the most recently evolved TEs along primate evolution, including not only SVAs but also younger Alu, LINE-L1 or LTR repeats. Conversely, H1.2, H1.3, H1.5, H1.0 are enriched in older TEs. Confocal and super-resolution microscopy experiments further confirm the differential distribution of H1 variants and their distinct contribution to chromatin structure. H1.2, H1.3 and H1.5 are enriched towards the nuclear periphery or lamina-associated domains. H1.4 and H1X show a punctuated pattern throughout the nucleus, with H1X being particularly enriched at nucleoli. H1.0 forms enrichment territories that tend to be peripheral. Moreover, depletion of H1.2, either alone or in combination with H1.4, leads to a general chromatin decompaction that is not observed upon single H1.4 or H1X depletion. Extensive analysis of multiple cell lines revealed the existence of certain universal distribution features despite variations in the H1 somatic repertoire. Specifically, H1.2, H1.3 and H1.5 consistently show enrichments towards the nuclear periphery in all cell lines examined, suggesting their universal role as components of lamina-associated domains. H1X, whose nucleolar presence is evident in all cell lines, is enriched at high- GC regions and younger SVA and Alu elements, as observed in T47D cells. In conclusion, we provide the first systematic comparison of six endogenous H1 variants within a mammalian cell type, while also addressing their differential distribution among multiple cell lines. Altogether, our results support H1 variants heterogeneity and highlight their significance as key organizers and regulators of chromatin.
publishDate 2023
dc.date.none.fl_str_mv 2023
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/2445/202890
http://hdl.handle.net/10803/689137
url https://hdl.handle.net/2445/202890
http://hdl.handle.net/10803/689137
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv cc by-nc-nd (c) Salinas Pena, Mónica, 2023
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc-nd (c) Salinas Pena, Mónica, 2023
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
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
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score 15.300719

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