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Molecular and Cellular Biology, November 2009, p. 5813-5827, Vol. 29, No. 21
0270-7306/09/$08.00+0     doi:10.1128/MCB.00670-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Blimp-1/Prdm1 Alternative Promoter Usage during Mouse Development and Plasma Cell Differentiation{triangledown}

Marc A. J. Morgan,1 Erna Magnusdottir,2 Tracy C. Kuo,2 Chai Tunyaplin,2 James Harper,1 Sebastian J. Arnold,1 Kathryn Calame,2 Elizabeth J. Robertson,1 and Elizabeth K. Bikoff1*

Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom,1 Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, New York 100322

Received 23 May 2009/ Returned for modification 11 July 2009/ Accepted 22 August 2009

The zinc-finger PR domain transcriptional repressor Blimp-1/Prdm1 plays essential roles in primordial germ cell specification, placental, heart, and forelimb development, plasma cell differentiation, and T-cell homeostasis. The present experiments demonstrate that the mouse Prdm1 gene has three alternative promoter regions. All three alternative first exons splice directly to exon 3, containing the translational start codon. To examine possible cell-type-specific functional activities in vivo, we generated targeted deletions that selectively eliminate two of these transcriptional start sites. Remarkably, mice lacking the previously described first exon develop normally and are fertile. However, this region contains NF-{kappa}B binding sites, and as shown here, NF-{kappa}B signaling is required for Prdm1 induction. Thus, mutant B cells fail to express Prdm1 in response to lipopolysaccharide stimulation and lack the ability to become antibody-secreting cells. An alternative distal promoter located ~70 kb upstream, giving rise to transcripts strongly expressed in the yolk sac, is dispensable. Thus, the deletion of exon 1B has no noticeable effect on expression levels in the embryo or adult tissues. Collectively, these experiments provide insight into the organization of the Prdm1 gene and demonstrate that NF-{kappa}B is a key mediator of Prdm1 expression.

* Corresponding author. Mailing address: University of Oxford, Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, United Kingdom. Phone: 0044 1865 285649. Fax: 44-1865-285492. E-mail: elizabeth.bikoff{at}path.ox.ac.uk

{triangledown} Published ahead of print on 8 September 2009.

Molecular and Cellular Biology, November 2009, p. 5813-5827, Vol. 29, No. 21
0270-7306/09/$08.00+0     doi:10.1128/MCB.00670-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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