Maintenance of Xist Imprinting Depends on Chromatin Condensation State and Rnf12 Dosage in Mice.
In female mammals, activation of Xist (X-inactive specific transcript) is essential for establishment of X chromosome inactivation. During early embryonic development in mice, paternal Xist is preferentially expressed whereas maternal Xist (Xm-Xist) is silenced. Unlike autosomal imprinted genes, Xis...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-10-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC5082930?pdf=render |
| _version_ | 1828239931096432640 |
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| author | Atsushi Fukuda Atsushi Mitani Toshiyuki Miyashita Takashi Sado Akihiro Umezawa Hidenori Akutsu |
| author_facet | Atsushi Fukuda Atsushi Mitani Toshiyuki Miyashita Takashi Sado Akihiro Umezawa Hidenori Akutsu |
| author_sort | Atsushi Fukuda |
| collection | DOAJ |
| description | In female mammals, activation of Xist (X-inactive specific transcript) is essential for establishment of X chromosome inactivation. During early embryonic development in mice, paternal Xist is preferentially expressed whereas maternal Xist (Xm-Xist) is silenced. Unlike autosomal imprinted genes, Xist imprinting for Xm-Xist silencing was erased in cloned or parthenogenetic but not fertilized embryos. However, the molecular mechanism underlying the variable nature of Xm-Xist imprinting is poorly understood. Here, we revealed that Xm-Xist silencing depends on chromatin condensation states at the Xist/Tsix genomic region and on Rnf12 expression levels. In early preimplantation, chromatin decondensation via H3K9me3 loss and histone acetylation gain caused Xm-Xist derepression irrespective of embryo type. Although the presence of the paternal genome during pronuclear formation impeded Xm-Xist derepression, Xm-Xist was robustly derepressed when the maternal genome was decondensed before fertilization. Once Xm-Xist was derepressed by chromatin alterations, the derepression was stably maintained and rescued XmXpΔ lethality, indicating that loss of Xm-Xist imprinting was irreversible. In late preimplantation, Oct4 served as a chromatin opener to create transcriptional permissive states at Xm-Xist/Tsix genomic loci. In parthenogenetic embryos, Rnf12 overdose caused Xm-Xist derepression via Xm-Tsix repression; physiological Rnf12 levels were essential for Xm-Xist silencing maintenance in fertilized embryos. Thus, chromatin condensation and fine-tuning of Rnf12 dosage were crucial for Xist imprint maintenance by silencing Xm-Xist. |
| first_indexed | 2024-04-12T21:31:05Z |
| format | Article |
| id | doaj.art-67535ad785524be781ce2fe387356fc6 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-04-12T21:31:05Z |
| publishDate | 2016-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-67535ad785524be781ce2fe387356fc62022-12-22T03:16:01ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042016-10-011210e100637510.1371/journal.pgen.1006375Maintenance of Xist Imprinting Depends on Chromatin Condensation State and Rnf12 Dosage in Mice.Atsushi FukudaAtsushi MitaniToshiyuki MiyashitaTakashi SadoAkihiro UmezawaHidenori AkutsuIn female mammals, activation of Xist (X-inactive specific transcript) is essential for establishment of X chromosome inactivation. During early embryonic development in mice, paternal Xist is preferentially expressed whereas maternal Xist (Xm-Xist) is silenced. Unlike autosomal imprinted genes, Xist imprinting for Xm-Xist silencing was erased in cloned or parthenogenetic but not fertilized embryos. However, the molecular mechanism underlying the variable nature of Xm-Xist imprinting is poorly understood. Here, we revealed that Xm-Xist silencing depends on chromatin condensation states at the Xist/Tsix genomic region and on Rnf12 expression levels. In early preimplantation, chromatin decondensation via H3K9me3 loss and histone acetylation gain caused Xm-Xist derepression irrespective of embryo type. Although the presence of the paternal genome during pronuclear formation impeded Xm-Xist derepression, Xm-Xist was robustly derepressed when the maternal genome was decondensed before fertilization. Once Xm-Xist was derepressed by chromatin alterations, the derepression was stably maintained and rescued XmXpΔ lethality, indicating that loss of Xm-Xist imprinting was irreversible. In late preimplantation, Oct4 served as a chromatin opener to create transcriptional permissive states at Xm-Xist/Tsix genomic loci. In parthenogenetic embryos, Rnf12 overdose caused Xm-Xist derepression via Xm-Tsix repression; physiological Rnf12 levels were essential for Xm-Xist silencing maintenance in fertilized embryos. Thus, chromatin condensation and fine-tuning of Rnf12 dosage were crucial for Xist imprint maintenance by silencing Xm-Xist.http://europepmc.org/articles/PMC5082930?pdf=render |
| spellingShingle | Atsushi Fukuda Atsushi Mitani Toshiyuki Miyashita Takashi Sado Akihiro Umezawa Hidenori Akutsu Maintenance of Xist Imprinting Depends on Chromatin Condensation State and Rnf12 Dosage in Mice. PLoS Genetics |
| title | Maintenance of Xist Imprinting Depends on Chromatin Condensation State and Rnf12 Dosage in Mice. |
| title_full | Maintenance of Xist Imprinting Depends on Chromatin Condensation State and Rnf12 Dosage in Mice. |
| title_fullStr | Maintenance of Xist Imprinting Depends on Chromatin Condensation State and Rnf12 Dosage in Mice. |
| title_full_unstemmed | Maintenance of Xist Imprinting Depends on Chromatin Condensation State and Rnf12 Dosage in Mice. |
| title_short | Maintenance of Xist Imprinting Depends on Chromatin Condensation State and Rnf12 Dosage in Mice. |
| title_sort | maintenance of xist imprinting depends on chromatin condensation state and rnf12 dosage in mice |
| url | http://europepmc.org/articles/PMC5082930?pdf=render |
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