Blimp-1/Prdm1 Alternative Promoter Usage during Mouse Development and Plasma Cell Differentiation
- 1 November 2009
- journal article
- research article
- Published by Taylor & Francis Ltd in Molecular and Cellular Biology
- Vol. 29 (21), 5813-5827
- https://doi.org/10.1128/mcb.00670-09
Abstract
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-κB binding sites, and as shown here, NF-κB 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-κB is a key mediator of Prdm1 expression.Keywords
This publication has 84 references indexed in Scilit:
- CTCF: Master Weaver of the GenomeCell, 2009
- The UCSC Genome Browser Database: update 2009Nucleic Acids Research, 2008
- Epidermal terminal differentiation depends on B lymphocyte-induced maturation protein-1Proceedings of the National Academy of Sciences of the United States of America, 2007
- Genome-wide maps of chromatin state in pluripotent and lineage-committed cellsNature, 2007
- Analysis of the Vertebrate Insulator Protein CTCF-Binding Sites in the Human GenomeCell, 2007
- Integrating cell-signalling pathways with NF-κB and IKK functionNature Reviews Molecular Cell Biology, 2007
- Blimp1 Defines a Progenitor Population that Governs Cellular Input to the Sebaceous GlandCell, 2006
- A Bivalent Chromatin Structure Marks Key Developmental Genes in Embryonic Stem CellsCell, 2006
- BLAT—The BLAST-Like Alignment ToolGenome Research, 2002
- Activators and target genes of Rel/NF-κB transcription factorsOncogene, 1999