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Molecular and Cellular Biology, April 2006, p. 3194-3203, Vol. 26, No. 8
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.8.3194-3203.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Transcription Elongation Factor S-II Is Required for Definitive Hematopoiesis

Takahiro Ito,1,{dagger} Nagisa Arimitsu,1,{dagger} Masaki Takeuchi,2,{dagger} Nobuyuki Kawamura,1 Makiko Nagata,1 Kayoko Saso,1 Nobuyoshi Akimitsu,1 Hiroshi Hamamoto,1 Shunji Natori,1 Atsushi Miyajima,2 and Kazuhisa Sekimizu1*

Division of Developmental Biochemistry, Graduate School of Pharmaceutical Sciences,1 Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo, Tokyo 113-0033, Japan2

Received 20 December 2005/ Accepted 27 January 2006

Transcription elongation factor S-II/TFIIS promotes readthrough of transcriptional blocks by stimulating nascent RNA cleavage activity of RNA polymerase II in vitro. The biologic significance of S-II function in higher eukaryotes, however, remains unclear. To determine its role in mammalian development, we generated S-II-deficient mice through targeted gene disruption. Homozygous null mutants died at midgestation with marked pallor, suggesting severe anemia. S-II–/– embryos had a decreased number of definitive erythrocytes in the peripheral blood and disturbed erythroblast differentiation in fetal liver. There was a dramatic increase in apoptotic cells in S-II–/– fetal liver, which was consistent with a reduction in Bcl-xL gene expression. The presence of phenotypically defined hematopoietic stem cells and in vitro colony-forming hematopoietic progenitors in S-II–/– fetal liver indicates that S-II is dispensable for the generation and differentiation of hematopoietic stem cells. S-II-deficient fetal liver cells, however, exhibited a loss of long-term repopulating potential when transplanted into lethally irradiated adult mice, indicating that S-II deficiency causes an intrinsic defect in the self-renewal of hematopoietic stem cells. Thus, S-II has critical and nonredundant roles in definitive hematopoiesis.

* Corresponding author. Mailing address: Division of Developmental Biochemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Hongo 7-3-1, Bunkyo, Tokyo 113-0033. Phone: 81-3-5841-4820. Fax: 81-3-5684-2973. E-mail: sekimizu{at}mol.f.u-tokyo.ac.jp.

{dagger} These authors contributed equally to this work.

Molecular and Cellular Biology, April 2006, p. 3194-3203, Vol. 26, No. 8
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.8.3194-3203.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Nagata, M., Ito, T., Arimitsu, N., Koyama, H., Sekimizu, K. (2009). Transcription arrest relief by S-II/TFIIS during gene expression in erythroblast differentiation. GENES CELLS 14: 371-380 [Abstract] [Full Text]  


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