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タイトル: | Srf destabilizes cellular identity by suppressing cell-type-specific gene expression programs |
著者: | Ikeda, Takashi Hikichi, Takafusa Miura, Hisashi Shibata, Hirofumi Mitsunaga, Kanae https://orcid.org/0000-0001-9631-6795 (unconfirmed) Yamada, Yosuke https://orcid.org/0000-0001-7952-2706 (unconfirmed) Woltjen, Knut https://orcid.org/0000-0003-2293-1183 (unconfirmed) Miyamoto, Kei Hiratani, Ichiro Yamada, Yasuhiro Hotta, Akitsu https://orcid.org/0000-0002-2619-7441 (unconfirmed) Yamamoto, Takuya https://orcid.org/0000-0002-0022-3947 (unconfirmed) Okita, Keisuke https://orcid.org/0000-0001-5806-1090 (unconfirmed) Masui, Shinji |
著者名の別形: | 池田, 隆 引地, 貴亮 柴田, 博史 光永, 佳奈枝 山田, 洋介 山田, 泰広 堀田, 秋津 山本, 拓也 沖田, 圭介 升井, 伸治 |
発行日: | 11-Apr-2018 |
出版者: | Springer Nature |
誌名: | Nature Communications |
巻: | 9 |
論文番号: | 1387 |
抄録: | Multicellular organisms consist of multiple cell types. The identity of these cells is primarily maintained by cell-type-specific gene expression programs; however, mechanisms that suppress these programs are poorly defined. Here we show that serum response factor (Srf), a transcription factor that is activated by various extracellular stimuli, can repress cell-type-specific genes and promote cellular reprogramming to pluripotency. Manipulations that decrease β-actin monomer quantity result in the nuclear accumulation of Mkl1 and the activation of Srf, which downregulate cell-type-specific genes and alter the epigenetics of regulatory regions and chromatin organization. Mice overexpressing Srf exhibit various pathologies including an ulcerative colitis-like symptom and a metaplasia-like phenotype in the pancreas. Our results demonstrate an unexpected function of Srf via a mechanism by which extracellular stimuli actively destabilize cell identity and suggest Srf involvement in a wide range of diseases. |
著作権等: | © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
URI: | http://hdl.handle.net/2433/234240 |
DOI(出版社版): | 10.1038/s41467-018-03748-1 |
PubMed ID: | 29643333 |
出現コレクション: | 学術雑誌掲載論文等 |
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