Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Transformation, Neoplastic / metabolism*
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DNA Footprinting
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DNA-Binding Proteins / metabolism*
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Humans
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Mice
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Plasmacytoma / metabolism*
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Positive Regulatory Domain I-Binding Factor 1
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-bcl-6
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Repressor Proteins / biosynthesis
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Repressor Proteins / genetics*
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STAT3 Transcription Factor
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Trans-Activators / metabolism
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Transcription Factors / biosynthesis
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Transcription Factors / genetics*
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Transcription Factors / metabolism*
Substances
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DNA-Binding Proteins
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Prdm1 protein, mouse
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-6
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Repressor Proteins
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STAT3 Transcription Factor
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STAT3 protein, human
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Stat3 protein, mouse
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Trans-Activators
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Transcription Factors
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PRDM1 protein, human
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Positive Regulatory Domain I-Binding Factor 1