Srf destabilizes cellular identity by suppressing cell-type-specific gene expression programs

Takashi Ikeda (), Takafusa Hikichi, Hisashi Miura, Hirofumi Shibata, Kanae Mitsunaga, Yosuke Yamada, Knut Woltjen, Kei Miyamoto, Ichiro Hiratani, Yasuhiro Yamada, Akitsu Hotta, Takuya Yamamoto, Keisuke Okita () and Shinji Masui ()
Additional contact information
Takashi Ikeda: Kyoto University
Takafusa Hikichi: Kyoto University
Hisashi Miura: RIKEN Center for Developmental Biology (CDB)
Hirofumi Shibata: Kyoto University
Kanae Mitsunaga: Kyoto University
Yosuke Yamada: Kyoto University
Knut Woltjen: Kyoto University
Kei Miyamoto: Kindai University
Ichiro Hiratani: RIKEN Center for Developmental Biology (CDB)
Yasuhiro Yamada: Kyoto University
Akitsu Hotta: Kyoto University
Takuya Yamamoto: Kyoto University
Keisuke Okita: Kyoto University
Shinji Masui: Kyoto University

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-03748-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03748-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-03748-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().