Direct repression of prdm1 by Bcl-6 inhibits plasmacytic differentiation.
We have identified two intronic regions of mouse prdm1, the gene encoding B lymphocyte-induced maturation protein-1 (Blimp-1), which confer transcriptional repression in response to Bcl-6. The Bcl-6 response element in intron 5, which is conserved between mice and humans, was studied in detail. It binds Bcl-6 in vitro and was shown by chromatin immunoprecipitation to be occupied by Bcl-6 in vivo. Neither Bcl-6 response element functions as a STAT3-response element, showing that STAT3 does not compete with Bcl-6 at these sites. Bcl-6(-/-) mice confirm the biological importance of Bcl-6-dependent repression of prdm1. These mice have elevated Ab response, increased Ig-secreting cells, and increased Blimp-1(+) cells in spleen following immunization and their splenic B cells show accelerated plasmacytic development in vitro.
Tunyaplin
Chainarong
C
Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Shaffer
A L
AL
Angelin-Duclos
Cristina D
CD
Yu
Xin
X
Staudt
Louis M
LM
Calame
Kathryn L
KL
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D010954:Plasmacytoma / Q000378:metabolism*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*
D004268:DNA-Binding Proteins; C513258:Prdm1 protein, mouse; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1