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Molecular and Cellular Biology, March 2009, p. 1421-1431, Vol. 29, No. 6
0270-7306/09/$08.00+0     doi:10.1128/MCB.01158-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Involvement of Histone Demethylase LSD1 in Blimp-1-Mediated Gene Repression during Plasma Cell Differentiation{triangledown}

Shin-Tang Su,1,2 Hsia-Yuan Ying,2,3 Yi-Kai Chiu,2,4 Fan-Ru Lin,1,2 Mei-Yu Chen,2 and Kuo-I Lin1,2*

Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan,1 Genomics Research Center, Academia Sinica, Taipei 115, Taiwan,2 Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan,3 Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan4

Received 22 July 2008/ Returned for modification 5 September 2008/ Accepted 19 December 2008

Plasma cell differentiation is orchestrated by the transcriptional repressor B lymphocyte-induced maturation protein-1 (Blimp-1), which silences the gene expression program of mature B cells. The molecular mechanism underlying Blimp-1 suppression of mature B-cell gene expression is not fully understood. Here we report that a proline-rich domain in Blimp-1 directly interacts with LSD1, a histone lysine demethylase. Both LSD1 knockdown and expression of Blimp-1 lacking the proline-rich domain derepressed the activities of Blimp-1-dependent luciferase reporters. Disruption of the Blimp-1 interaction with LSD1 or reduced LSD1 expression attenuated antibody production, demonstrating the biological significance of this interaction. Finally, using chromatin immunoprecipitation, we showed that Blimp-1 binding to its target sites is accompanied by LSD1 binding to those same sites and that LSD1 binding correlates with histone modifications of accessible chromatin. These findings provide further insights into the molecular mechanism of the silencing of mature B-cell genes by Blimp-1 in plasma cell differentiation.

* Corresponding author. Mailing address: Genomics Research Center, Academia Sinica, 128 Academia Road, Sec. 2, Nankang Dist., Taipei 115, Taiwan. Phone: 886-2-2787-1253. Fax: 886-2-2789-9931. E-mail: kuoilin{at}gate.sinica.edu.tw

{triangledown} Published ahead of print on 5 January 2009.

Molecular and Cellular Biology, March 2009, p. 1421-1431, Vol. 29, No. 6
0270-7306/09/$08.00+0     doi:10.1128/MCB.01158-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Chan, Y.-H., Chiang, M.-F., Tsai, Y.-C., Su, S.-T., Chen, M.-H., Hou, M.-S., Lin, K.-I (2009). Absence of the Transcriptional Repressor Blimp-1 in Hematopoietic Lineages Reveals Its Role in Dendritic Cell Homeostatic Development and Function. J. Immunol. 183: 7039-7046 [Abstract] [Full Text]  
  • Barnes, N. A., Stephenson, S. J., Tooze, R. M., Doody, G. M. (2009). Amino Acid Deprivation Links BLIMP-1 to the Immunomodulatory Enzyme Indoleamine 2,3-Dioxygenase. J. Immunol. 183: 5768-5777 [Abstract] [Full Text]  


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