Large hypomethylated domains serve as strong repressive machinery for key developmental genes in vertebrates
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- Ryohei Nakamura
- Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan
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- Tatsuya Tsukahara
- Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan
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- Wei Qu
- Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa 277-0882, Japan
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- Kazuki Ichikawa
- Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa 277-0882, Japan
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- Takayoshi Otsuka
- Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan
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- Katsumi Ogoshi
- Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
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- Taro L. Saito
- Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa 277-0882, Japan
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- Kouji Matsushima
- Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
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- Sumio Sugano
- Department of Medical Genome, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8561, Japan
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- Shinichi Hashimoto
- Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
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- Yutaka Suzuki
- Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa 277-0882, Japan
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- Shinichi Morishita
- Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa 277-0882, Japan
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- Hiroyuki Takeda
- Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan
抄録
<jats:p>DNA methylation is a fundamental epigenetic modification in vertebrate genomes and a small fraction of genomic regions is hypomethylated. Previous studies have implicated hypomethylated regions in gene regulation, but their functions in vertebrate development remain elusive. To address this issue, we generated epigenomic profiles that include base-resolution DNA methylomes and histone modification maps from both pluripotent cells and mature organs of medaka fish and compared the profiles with those of human ES cells. We found that a subset of hypomethylated domains harbor H3K27me3 (K27HMDs) and their size positively correlates with the accumulation of H3K27me3. Large K27HMDs are conserved between medaka and human pluripotent cells and predominantly contain promoters of developmental transcription factor genes. These key genes were found to be under strong transcriptional repression, when compared with other developmental genes with smaller K27HMDs. Furthermore, human-specific K27HMDs show an enrichment of neuronal activity-related genes, which suggests a distinct regulation of these genes in medaka and human. In mature organs, some of the large HMDs become shortened by elevated DNA methylation and associate with sustained gene expression. This study highlights the significance of domain size in epigenetic gene regulation. We propose that large K27HMDs play a crucial role in pluripotent cells by strictly repressing key developmental genes, whereas their shortening consolidates long-term gene expression in adult differentiated cells.</jats:p>
収録刊行物
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- Development
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Development 141 (13), 2568-2580, 2014-07-01
The Company of Biologists
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詳細情報 詳細情報について
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- CRID
- 1360285711954798208
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- ISSN
- 14779129
- 09501991
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- データソース種別
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- Crossref
- KAKEN