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The histone variant H3.3 G34W substitution in giant cell tumor of the bone link chromatin and RNA processing
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| Veröffentlicht in: | Scientific reports 7(2017) Article number: 13459, 14 Seiten |
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| Personen und Körperschaften: | , , , |
| Titel: | The histone variant H3.3 G34W substitution in giant cell tumor of the bone link chromatin and RNA processing/ Jinyeong Lim, Joo Hyun Park, Annika Baude, Yeongran Yoo, Yeon Kyu Lee, Christopher R. Schmidt, Jong Bae Park, Jörg Fellenberg, Josef Zustin, Florian Haller, Irene Krücken, Hyun Guy Kang, Yoon Jung Park, Christoph Plass & Anders M. Lindroth |
| Format: | E-Book-Kapitel |
| Sprache: | Englisch |
| veröffentlicht: |
18 October 2017
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| Gesamtaufnahme: |
: Scientific reports, 7(2017) Article number: 13459, 14 Seiten
, volume:7 |
| Quelle: | Verbunddaten SWB Lizenzfreie Online-Ressourcen |
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| 520 | |a While transcription as regulated by histones and their post-translational modifications has been well described, the function of histone variants in this process remains poorly characterized. Potentially important insight into this process pertain to the frequently occurring mutations of H3.3, leading to G34 substitutions in childhood glioblastoma and giant cell tumor of the bone (GCTB). In this study, we have established primary cell lines from GCTB patients and used them to uncover the influence of H3.3 G34W substitutions on cellular growth behavior, gene expression, and chromatin compaction. Primary cell lines with H3.3 G34W showed increased colony formation, infiltration and proliferation, known hallmarks of tumor development. Isogenic cell lines with H3.3 G34W recapitulated the increased proliferation observed in primary cells. Transcriptomic analysis of primary cells and tumor biopsies revealed slightly more downregulated gene expression, perhaps by increased chromatin compaction. We identified components related to splicing, most prominently hnRNPs, by immunoprecipitation and mass spectrometry that specifically interact with H3.3 G34W in the isogenic cell lines. RNA-sequencing analysis and hybridization-based validations further enforced splicing aberrations. Our data uncover a role for H3.3 in RNA processing and chromatin modulation that is blocked by the G34W substitution, potentially driving the tumorigenic process in GCTB. | ||
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| contents | While transcription as regulated by histones and their post-translational modifications has been well described, the function of histone variants in this process remains poorly characterized. Potentially important insight into this process pertain to the frequently occurring mutations of H3.3, leading to G34 substitutions in childhood glioblastoma and giant cell tumor of the bone (GCTB). In this study, we have established primary cell lines from GCTB patients and used them to uncover the influence of H3.3 G34W substitutions on cellular growth behavior, gene expression, and chromatin compaction. Primary cell lines with H3.3 G34W showed increased colony formation, infiltration and proliferation, known hallmarks of tumor development. Isogenic cell lines with H3.3 G34W recapitulated the increased proliferation observed in primary cells. Transcriptomic analysis of primary cells and tumor biopsies revealed slightly more downregulated gene expression, perhaps by increased chromatin compaction. We identified components related to splicing, most prominently hnRNPs, by immunoprecipitation and mass spectrometry that specifically interact with H3.3 G34W in the isogenic cell lines. RNA-sequencing analysis and hybridization-based validations further enforced splicing aberrations. Our data uncover a role for H3.3 in RNA processing and chromatin modulation that is blocked by the G34W substitution, potentially driving the tumorigenic process in GCTB. |
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| spelling | Lim, Jinyeong VerfasserIn (DE-588)1167531949 (DE-627)1031158545 (DE-576)511179197 aut, The histone variant H3.3 G34W substitution in giant cell tumor of the bone link chromatin and RNA processing Jinyeong Lim, Joo Hyun Park, Annika Baude, Yeongran Yoo, Yeon Kyu Lee, Christopher R. Schmidt, Jong Bae Park, Jörg Fellenberg, Josef Zustin, Florian Haller, Irene Krücken, Hyun Guy Kang, Yoon Jung Park, Christoph Plass & Anders M. Lindroth, 18 October 2017, 14, Text txt rdacontent, Computermedien c rdamedia, Online-Ressource cr rdacarrier, Gesehen am 21.09.2018, While transcription as regulated by histones and their post-translational modifications has been well described, the function of histone variants in this process remains poorly characterized. Potentially important insight into this process pertain to the frequently occurring mutations of H3.3, leading to G34 substitutions in childhood glioblastoma and giant cell tumor of the bone (GCTB). In this study, we have established primary cell lines from GCTB patients and used them to uncover the influence of H3.3 G34W substitutions on cellular growth behavior, gene expression, and chromatin compaction. Primary cell lines with H3.3 G34W showed increased colony formation, infiltration and proliferation, known hallmarks of tumor development. Isogenic cell lines with H3.3 G34W recapitulated the increased proliferation observed in primary cells. Transcriptomic analysis of primary cells and tumor biopsies revealed slightly more downregulated gene expression, perhaps by increased chromatin compaction. We identified components related to splicing, most prominently hnRNPs, by immunoprecipitation and mass spectrometry that specifically interact with H3.3 G34W in the isogenic cell lines. RNA-sequencing analysis and hybridization-based validations further enforced splicing aberrations. Our data uncover a role for H3.3 in RNA processing and chromatin modulation that is blocked by the G34W substitution, potentially driving the tumorigenic process in GCTB., Baude, Annika VerfasserIn (DE-588)1167532880 (DE-627)1031159355 (DE-576)511180055 aut, Fellenberg, Jörg VerfasserIn (DE-588)1063323932 (DE-627)812309219 (DE-576)171796543 aut, Plass, Christoph 1961- VerfasserIn (DE-588)116753347X (DE-627)1031159894 (DE-576)51118106X aut, Enthalten in Scientific reports [London] : Macmillan Publishers Limited, part of Springer Nature, 2011 7(2017) Article number: 13459, 14 Seiten Online-Ressource (DE-627)663366712 (DE-600)2615211-3 (DE-576)346641179 2045-2322 nnns, volume:7 year:2017 extent:14, http://dx.doi.org/10.1038/s41598-017-13887-y Verlag Resolving-System kostenfrei Volltext, https://www.nature.com/articles/s41598-017-13887-y Verlag kostenfrei Volltext, http://dx.doi.org/10.1038/s41598-017-13887-y LFER, LFER 2018-10-10T00:00:00Z |
| spellingShingle | Lim, Jinyeong, Baude, Annika, Fellenberg, Jörg, Plass, Christoph, The histone variant H3.3 G34W substitution in giant cell tumor of the bone link chromatin and RNA processing, While transcription as regulated by histones and their post-translational modifications has been well described, the function of histone variants in this process remains poorly characterized. Potentially important insight into this process pertain to the frequently occurring mutations of H3.3, leading to G34 substitutions in childhood glioblastoma and giant cell tumor of the bone (GCTB). In this study, we have established primary cell lines from GCTB patients and used them to uncover the influence of H3.3 G34W substitutions on cellular growth behavior, gene expression, and chromatin compaction. Primary cell lines with H3.3 G34W showed increased colony formation, infiltration and proliferation, known hallmarks of tumor development. Isogenic cell lines with H3.3 G34W recapitulated the increased proliferation observed in primary cells. Transcriptomic analysis of primary cells and tumor biopsies revealed slightly more downregulated gene expression, perhaps by increased chromatin compaction. We identified components related to splicing, most prominently hnRNPs, by immunoprecipitation and mass spectrometry that specifically interact with H3.3 G34W in the isogenic cell lines. RNA-sequencing analysis and hybridization-based validations further enforced splicing aberrations. Our data uncover a role for H3.3 in RNA processing and chromatin modulation that is blocked by the G34W substitution, potentially driving the tumorigenic process in GCTB. |
| swb_id_str | 511181248 |
| title | The histone variant H3.3 G34W substitution in giant cell tumor of the bone link chromatin and RNA processing |
| title_auth | The histone variant H3.3 G34W substitution in giant cell tumor of the bone link chromatin and RNA processing |
| title_full | The histone variant H3.3 G34W substitution in giant cell tumor of the bone link chromatin and RNA processing Jinyeong Lim, Joo Hyun Park, Annika Baude, Yeongran Yoo, Yeon Kyu Lee, Christopher R. Schmidt, Jong Bae Park, Jörg Fellenberg, Josef Zustin, Florian Haller, Irene Krücken, Hyun Guy Kang, Yoon Jung Park, Christoph Plass & Anders M. Lindroth |
| title_fullStr | The histone variant H3.3 G34W substitution in giant cell tumor of the bone link chromatin and RNA processing Jinyeong Lim, Joo Hyun Park, Annika Baude, Yeongran Yoo, Yeon Kyu Lee, Christopher R. Schmidt, Jong Bae Park, Jörg Fellenberg, Josef Zustin, Florian Haller, Irene Krücken, Hyun Guy Kang, Yoon Jung Park, Christoph Plass & Anders M. Lindroth |
| title_full_unstemmed | The histone variant H3.3 G34W substitution in giant cell tumor of the bone link chromatin and RNA processing Jinyeong Lim, Joo Hyun Park, Annika Baude, Yeongran Yoo, Yeon Kyu Lee, Christopher R. Schmidt, Jong Bae Park, Jörg Fellenberg, Josef Zustin, Florian Haller, Irene Krücken, Hyun Guy Kang, Yoon Jung Park, Christoph Plass & Anders M. Lindroth |
| title_in_hierarchy | The histone variant H3.3 G34W substitution in giant cell tumor of the bone link chromatin and RNA processing / Jinyeong Lim, Joo Hyun Park, Annika Baude, Yeongran Yoo, Yeon Kyu Lee, Christopher R. Schmidt, Jong Bae Park, Jörg Fellenberg, Josef Zustin, Florian Haller, Irene Krücken, Hyun Guy Kang, Yoon Jung Park, Christoph Plass & Anders M. Lindroth, |
| title_short | The histone variant H3.3 G34W substitution in giant cell tumor of the bone link chromatin and RNA processing |
| title_sort | the histone variant h3 3 g34w substitution in giant cell tumor of the bone link chromatin and rna processing |
| url | http://dx.doi.org/10.1038/s41598-017-13887-y, https://www.nature.com/articles/s41598-017-13887-y |