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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-kappaB binding sites, and as shown here, NF-kappaB 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 approximately 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-kappaB is a key mediator of Prdm1 expression.

Original publication

DOI

10.1128/MCB.00670-09

Type

Journal article

Journal

Mol Cell Biol

Publication Date

11/2009

Volume

29

Pages

5813 - 5827

Keywords

Animals, Base Pairing, Base Sequence, Cell Differentiation, Dendritic Cells, Embryonic Development, Exons, Gene Deletion, Gene Dosage, Gene Expression Regulation, Developmental, Gene Targeting, Heterozygote, Introns, Mice, Molecular Sequence Data, NF-kappa B, Plasma Cells, Promoter Regions, Genetic, Protein Binding, RNA, Messenger, Signal Transduction, T-Lymphocytes, Transcription Factors, Transcription Initiation Site, Transcriptional Activation