PMID:18845144

Citation	Schmidt, D, Nayak, A, Schumann, JE, Schimpl, A, Berberich, I and Berberich-Siebelt, F (2008) Blimp-1Deltaexon7: a naturally occurring Blimp-1 deletion mutant with auto-regulatory potential. Exp. Cell Res. 314:3614-27
Abstract	Blimp-1 is a master regulator of terminal B cell differentiation and plays a pivotal role in various developmental processes. In addition to full length Blimp-1, a Blimp-1 mRNA lacking exon 7 (Blimp-1Delta7) has been described to occur in murine B cells. The activity and function of the mutant mRNA-encoded protein (Blimp-1Delta7), lacking three crucial zinc fingers necessary for DNA interaction, is completely unknown. Since isoforms of other prdm family proteins affect each other's functions, we wondered whether Blimp-1Delta7 still plays a role in B cells, independent of direct DNA binding. In this study, we found that Blimp-1Delta7 is preferentially expressed in naïve CD19(+) B cells. A fraction of Blimp-1Delta7 migrates to the nucleus, colocalizes with HDAC2 and is found at sites of repressed chromatin, although it does not bind to the Blimp-1 DNA consensus site. Unexpectedly, Blimp-1 and Blimp-1Delta7 homodimerize as well as heterodimerize with each other. Ectopic expression of Blimp-1Delta7 in WEHI 231 cells, a Blimp-1-negative murine lymphoma line, leads to cessation of proliferation and enhancement of apoptosis. Importantly, LPS-induced differentiation is suppressed in the presence of Blimp-1Delta7. This is in agreement with our finding that Blimp-1Delta7 interferes with endogenous Blimp-1 expression. Thus, our data suggest an auto-regulatory mechanism of Blimp-1 activation.
Links	PubMed Online version:10.1016/j.yexcr.2008.09.008
Keywords	Animals; Antigens, CD19/metabolism; Apoptosis/genetics; Autocrine Communication/genetics; B-Lymphocytes/metabolism; Cell Cycle/genetics; Cells, Cultured; Exons; Gene Deletion; Gene Expression Regulation; Humans; Mice; Mice, Inbred C57BL; Mutant Proteins/genetics; Mutant Proteins/metabolism; Mutant Proteins/physiology; Protein Isoforms/genetics; Protein Isoforms/metabolism; Protein Isoforms/physiology; RNA, Messenger/metabolism; Transcription Factors/genetics; Transcription Factors/metabolism; Transcription Factors/physiology; Transfection
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:PRDM1	acts_upstream_of_or_within	GO:0045579: positive regulation of B cell differentiation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:PRDM1	enables	GO:0043565: sequence-specific DNA binding	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
MOUSE:PRDM1	part_of	GO:0005634: nucleus	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
MOUSE:PRDM1	NOT|acts_upstream_of_or_within	GO:0045579: positive regulation of B cell differentiation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:PRDM1	enables	GO:0042826: histone deacetylase binding	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
MOUSE:PRDM1	acts_upstream_of_or_within	GO:0031665: negative regulation of lipopolysaccharide-mediated signaling pathway	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:PRDM1	acts_upstream_of_or_within	GO:0030889: negative regulation of B cell proliferation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:PRDM1	part_of	GO:0005737: cytoplasm	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
MOUSE:PRDM1	acts_upstream_of_or_within	GO:0000122: negative regulation of transcription by RNA polymerase II	ECO:0000314: direct assay evidence used in manual assertion		P	has_regulation_target:(MGI:MGI:99655)	Seeded From UniProt	complete

References

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