論文 - 詳細
| RRC ID | 47249 |
|---|---|
| 著者 | Fukuda A, Mitani A, Miyashita T, Sado T, Umezawa A, Akutsu H. |
| タイトル | Maintenance of Xist Imprinting Depends on Chromatin Condensation State and Rnf12 Dosage in Mice. |
| ジャーナル | PLoS Genet |
| Abstract |
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. |
| 巻・号 | 12(10) |
| ページ | e1006375 |
| 公開日 | 2016-10-1 |
| DOI | 10.1371/journal.pgen.1006375 |
| PII | PGENETICS-D-16-01173 |
| PMID | 27788132 |
| PMC | PMC5082930 |
| MeSH | Animals Blastocyst Chromatin / genetics* Female Gene Dosage Gene Expression Regulation, Developmental Gene Silencing Genomic Imprinting Maternal Inheritance / genetics Mice Octamer Transcription Factor-3 / genetics* Parthenogenesis / genetics Paternal Inheritance / genetics RNA, Long Noncoding / biosynthesis RNA, Long Noncoding / genetics* Ubiquitin-Protein Ligases / biosynthesis Ubiquitin-Protein Ligases / genetics* X Chromosome Inactivation / genetics* |
| IF | 5.175 |
| 引用数 | 4 |
| WOS 分野 | GENETICS & HEREDITY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 13 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC02655 |