Chromatin environment-dependent effects of DOT1L on gene expression in male germ cells
Abstract The H3K79 methyltransferase DOT1L is essential for multiple aspects of mammalian development where it has been shown to regulate gene expression. Here, by producing and integrating epigenomic and spike-in RNA-seq data, we decipher the molecular role of DOT1L during mouse spermatogenesis and...
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Nature Portfolio
2025-01-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-07393-x |
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| author | Manon Coulée Alberto de la Iglesia Mélina Blanco Clara Gobé Clémentine Lapoujade Côme Ialy-Radio Lucia Alvarez-Gonzalez Guillaume Meurice Aurora Ruiz-Herrera Pierre Fouchet Julie Cocquet Laïla El Khattabi |
| author_facet | Manon Coulée Alberto de la Iglesia Mélina Blanco Clara Gobé Clémentine Lapoujade Côme Ialy-Radio Lucia Alvarez-Gonzalez Guillaume Meurice Aurora Ruiz-Herrera Pierre Fouchet Julie Cocquet Laïla El Khattabi |
| author_sort | Manon Coulée |
| collection | DOAJ |
| description | Abstract The H3K79 methyltransferase DOT1L is essential for multiple aspects of mammalian development where it has been shown to regulate gene expression. Here, by producing and integrating epigenomic and spike-in RNA-seq data, we decipher the molecular role of DOT1L during mouse spermatogenesis and show that it has opposite effects on gene expression depending on chromatin environment. On one hand, DOT1L represses autosomal genes that are devoid of H3K79me2 at their bodies and located in H3K27me3-rich/H3K27ac-poor environments. On the other hand, it activates the expression of genes enriched in H3K79me2 and located in H3K27me3-poor/H3K27ac-rich environments, predominantly X chromosome-linked genes, after meiosis I. This coincides with a significant increase in DOT1L expression at this stage and a genome-wide acquisition of H3K79me2, particularly on the sex chromosomes. Taken together, our results show that H3K79me2 positively correlates with male germ cell genetic program throughout spermatogenesis, with DOT1L predominantly inhibiting rather than activating gene expression. Interestingly, while DOT1L appears to directly regulate the (re)activation of X genes following meiotic sex chromosome inactivation, it also controls the timely expression of (autosomal) differentiation genes during spermatogenesis. |
| format | Article |
| id | doaj-art-d80dea0a27134490b25e35359f2e23fe |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-d80dea0a27134490b25e35359f2e23fe2025-02-02T12:37:07ZengNature PortfolioCommunications Biology2399-36422025-01-018111710.1038/s42003-024-07393-xChromatin environment-dependent effects of DOT1L on gene expression in male germ cellsManon Coulée0Alberto de la Iglesia1Mélina Blanco2Clara Gobé3Clémentine Lapoujade4Côme Ialy-Radio5Lucia Alvarez-Gonzalez6Guillaume Meurice7Aurora Ruiz-Herrera8Pierre Fouchet9Julie Cocquet10Laïla El Khattabi11Université Paris Cité, CNRS, Inserm, Institut CochinUniversité Paris Cité, CNRS, Inserm, Institut CochinUniversité Paris Cité, CNRS, Inserm, Institut CochinUniversité Paris Cité, CNRS, Inserm, Institut CochinUniversité Paris Cité, CEA, Stabilité Génétique Cellules Souches et RadiationsUniversité Paris Cité, CNRS, Inserm, Institut CochinDepartament de Biologia Cel·lular, Fisiologia i Immunologia, Universitat Autònoma de BarcelonaMOABI, plateforme de Bioinformatique de l’APHPDepartament de Biologia Cel·lular, Fisiologia i Immunologia, Universitat Autònoma de BarcelonaUniversité Paris Cité, CEA, Stabilité Génétique Cellules Souches et RadiationsUniversité Paris Cité, CNRS, Inserm, Institut CochinUniversité Paris Cité, CNRS, Inserm, Institut CochinAbstract The H3K79 methyltransferase DOT1L is essential for multiple aspects of mammalian development where it has been shown to regulate gene expression. Here, by producing and integrating epigenomic and spike-in RNA-seq data, we decipher the molecular role of DOT1L during mouse spermatogenesis and show that it has opposite effects on gene expression depending on chromatin environment. On one hand, DOT1L represses autosomal genes that are devoid of H3K79me2 at their bodies and located in H3K27me3-rich/H3K27ac-poor environments. On the other hand, it activates the expression of genes enriched in H3K79me2 and located in H3K27me3-poor/H3K27ac-rich environments, predominantly X chromosome-linked genes, after meiosis I. This coincides with a significant increase in DOT1L expression at this stage and a genome-wide acquisition of H3K79me2, particularly on the sex chromosomes. Taken together, our results show that H3K79me2 positively correlates with male germ cell genetic program throughout spermatogenesis, with DOT1L predominantly inhibiting rather than activating gene expression. Interestingly, while DOT1L appears to directly regulate the (re)activation of X genes following meiotic sex chromosome inactivation, it also controls the timely expression of (autosomal) differentiation genes during spermatogenesis.https://doi.org/10.1038/s42003-024-07393-x |
| spellingShingle | Manon Coulée Alberto de la Iglesia Mélina Blanco Clara Gobé Clémentine Lapoujade Côme Ialy-Radio Lucia Alvarez-Gonzalez Guillaume Meurice Aurora Ruiz-Herrera Pierre Fouchet Julie Cocquet Laïla El Khattabi Chromatin environment-dependent effects of DOT1L on gene expression in male germ cells Communications Biology |
| title | Chromatin environment-dependent effects of DOT1L on gene expression in male germ cells |
| title_full | Chromatin environment-dependent effects of DOT1L on gene expression in male germ cells |
| title_fullStr | Chromatin environment-dependent effects of DOT1L on gene expression in male germ cells |
| title_full_unstemmed | Chromatin environment-dependent effects of DOT1L on gene expression in male germ cells |
| title_short | Chromatin environment-dependent effects of DOT1L on gene expression in male germ cells |
| title_sort | chromatin environment dependent effects of dot1l on gene expression in male germ cells |
| url | https://doi.org/10.1038/s42003-024-07393-x |
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