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Title: Srf destabilizes cellular identity by suppressing cell-type-specific gene expression programs
Authors: Ikeda, Takashi
Hikichi, Takafusa
Miura, Hisashi
Shibata, Hirofumi
Mitsunaga, Kanae
Yamada, Yosuke  kyouindb  KAKEN_id
Woltjen, Knut  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0003-2293-1183 (unconfirmed)
Miyamoto, Kei
Hiratani, Ichiro
Yamada, Yasuhiro
Hotta, Akitsu  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-2619-7441 (unconfirmed)
Yamamoto, Takuya  kyouindb  KAKEN_id
Okita, Keisuke  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0001-5806-1090 (unconfirmed)
Masui, Shinji
Author's alias: 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
Issue Date: 11-Apr-2018
Publisher: Springer Nature
Journal title: Nature Communications
Volume: 9
Thesis number: 1387
Abstract: 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.
Rights: © 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(Published Version): 10.1038/s41467-018-03748-1
PubMed ID: 29643333
Appears in Collections:Journal Articles

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