Nut Directs p300-Dependent, Genome-Wide H4 Hyperacetylation in Male Germ Cells
Summary: Nuclear protein in testis (Nut) is a universal oncogenic driver in the highly aggressive NUT midline carcinoma, whose physiological function in male germ cells has been unclear. Here we show that expression of Nut is normally restricted to post-meiotic spermatogenic cells, where its presenc...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-09-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718313731 |
| _version_ | 1818694731253678080 |
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| author | Hitoshi Shiota Sophie Barral Thierry Buchou Minjia Tan Yohann Couté Guillaume Charbonnier Nicolas Reynoird Fayçal Boussouar Matthieu Gérard Mingrui Zhu Lisa Bargier Denis Puthier Florent Chuffart Ekaterina Bourova-Flin Sarah Picaud Panagis Filippakopoulos Afsaneh Goudarzi Ziad Ibrahim Daniel Panne Sophie Rousseaux Yingming Zhao Saadi Khochbin |
| author_facet | Hitoshi Shiota Sophie Barral Thierry Buchou Minjia Tan Yohann Couté Guillaume Charbonnier Nicolas Reynoird Fayçal Boussouar Matthieu Gérard Mingrui Zhu Lisa Bargier Denis Puthier Florent Chuffart Ekaterina Bourova-Flin Sarah Picaud Panagis Filippakopoulos Afsaneh Goudarzi Ziad Ibrahim Daniel Panne Sophie Rousseaux Yingming Zhao Saadi Khochbin |
| author_sort | Hitoshi Shiota |
| collection | DOAJ |
| description | Summary: Nuclear protein in testis (Nut) is a universal oncogenic driver in the highly aggressive NUT midline carcinoma, whose physiological function in male germ cells has been unclear. Here we show that expression of Nut is normally restricted to post-meiotic spermatogenic cells, where its presence triggers p300-dependent genome-wide histone H4 hyperacetylation, which is essential for the completion of histone-to-protamine exchange. Accordingly, the inactivation of Nut induces male sterility with spermatogenesis arrest at the histone-removal stage. Nut uses p300 and/or CBP to enhance acetylation of H4 at both K5 and K8, providing binding sites for the first bromodomain of Brdt, the testis-specific member of the BET family, which subsequently mediates genome-wide histone removal. Altogether, our data reveal the detailed molecular basis of the global histone hyperacetylation wave, which occurs before the final compaction of the male genome. : A transcription-independent histone hyperacetylation is associated with near-total histone replacement during mouse spermatogenesis. Shiota et al. show the oncogenic factor Nut is expressed in post-meiotic male germ cells, where it recruits p300 and/or CBP and enhances histone H4K5 and H4K8 acetylation, leading to histone-to-protamine replacement. Keywords: BRD4-NUT, protamines, transition proteins, histone variants, spermiogenesis, histone post-translational modifications, cancer testis, testis specific |
| first_indexed | 2024-12-17T13:34:14Z |
| format | Article |
| id | doaj.art-df3c3fd21a274a8b95f2d28fef81b222 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-17T13:34:14Z |
| publishDate | 2018-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-df3c3fd21a274a8b95f2d28fef81b2222022-12-21T21:46:29ZengElsevierCell Reports2211-12472018-09-01241334773487.e6Nut Directs p300-Dependent, Genome-Wide H4 Hyperacetylation in Male Germ CellsHitoshi Shiota0Sophie Barral1Thierry Buchou2Minjia Tan3Yohann Couté4Guillaume Charbonnier5Nicolas Reynoird6Fayçal Boussouar7Matthieu Gérard8Mingrui Zhu9Lisa Bargier10Denis Puthier11Florent Chuffart12Ekaterina Bourova-Flin13Sarah Picaud14Panagis Filippakopoulos15Afsaneh Goudarzi16Ziad Ibrahim17Daniel Panne18Sophie Rousseaux19Yingming Zhao20Saadi Khochbin21CNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, FranceCNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, FranceCNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, FranceShanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, P.R. ChinaUniversité Grenoble Alpes, CEA, Inserm U1038, CEA, BIG-BGE, Grenoble 38000, FranceTGML, platform IbiSA, Aix Marseille Université, Inserm U1090, TAGC, Marseille, FranceCNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, FranceCNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, FranceCEA, iBiTec-S, Gif-sur-Yvette 91191, FranceShanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, P.R. ChinaTGML, platform IbiSA, Aix Marseille Université, Inserm U1090, TAGC, Marseille, FranceTGML, platform IbiSA, Aix Marseille Université, Inserm U1090, TAGC, Marseille, FranceCNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, FranceCNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, FranceStructural Genomics Consortium & Ludwig Institute for Cancer Research, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UKStructural Genomics Consortium & Ludwig Institute for Cancer Research, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UKCNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, FranceEMBL Grenoble, BP 181, 71 Avenue des Martyrs, 38042 Grenoble Cedex 9, FranceEMBL Grenoble, BP 181, 71 Avenue des Martyrs, 38042 Grenoble Cedex 9, France; Leicester Institute of Structural and Chemical Biology, Department of Molecular and Cell Biology, University of Leicester, Lancaster Road, Leicester LE1 7RH, UKCNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, FranceBen May Department of Cancer Research, The University of Chicago, Chicago, IL 60637, USACNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, France; Corresponding authorSummary: Nuclear protein in testis (Nut) is a universal oncogenic driver in the highly aggressive NUT midline carcinoma, whose physiological function in male germ cells has been unclear. Here we show that expression of Nut is normally restricted to post-meiotic spermatogenic cells, where its presence triggers p300-dependent genome-wide histone H4 hyperacetylation, which is essential for the completion of histone-to-protamine exchange. Accordingly, the inactivation of Nut induces male sterility with spermatogenesis arrest at the histone-removal stage. Nut uses p300 and/or CBP to enhance acetylation of H4 at both K5 and K8, providing binding sites for the first bromodomain of Brdt, the testis-specific member of the BET family, which subsequently mediates genome-wide histone removal. Altogether, our data reveal the detailed molecular basis of the global histone hyperacetylation wave, which occurs before the final compaction of the male genome. : A transcription-independent histone hyperacetylation is associated with near-total histone replacement during mouse spermatogenesis. Shiota et al. show the oncogenic factor Nut is expressed in post-meiotic male germ cells, where it recruits p300 and/or CBP and enhances histone H4K5 and H4K8 acetylation, leading to histone-to-protamine replacement. Keywords: BRD4-NUT, protamines, transition proteins, histone variants, spermiogenesis, histone post-translational modifications, cancer testis, testis specifichttp://www.sciencedirect.com/science/article/pii/S2211124718313731 |
| spellingShingle | Hitoshi Shiota Sophie Barral Thierry Buchou Minjia Tan Yohann Couté Guillaume Charbonnier Nicolas Reynoird Fayçal Boussouar Matthieu Gérard Mingrui Zhu Lisa Bargier Denis Puthier Florent Chuffart Ekaterina Bourova-Flin Sarah Picaud Panagis Filippakopoulos Afsaneh Goudarzi Ziad Ibrahim Daniel Panne Sophie Rousseaux Yingming Zhao Saadi Khochbin Nut Directs p300-Dependent, Genome-Wide H4 Hyperacetylation in Male Germ Cells Cell Reports |
| title | Nut Directs p300-Dependent, Genome-Wide H4 Hyperacetylation in Male Germ Cells |
| title_full | Nut Directs p300-Dependent, Genome-Wide H4 Hyperacetylation in Male Germ Cells |
| title_fullStr | Nut Directs p300-Dependent, Genome-Wide H4 Hyperacetylation in Male Germ Cells |
| title_full_unstemmed | Nut Directs p300-Dependent, Genome-Wide H4 Hyperacetylation in Male Germ Cells |
| title_short | Nut Directs p300-Dependent, Genome-Wide H4 Hyperacetylation in Male Germ Cells |
| title_sort | nut directs p300 dependent genome wide h4 hyperacetylation in male germ cells |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718313731 |
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