Direct Repression of prdm1 by Bcl-6 Inhibits Plasmacytic Differentiation
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.
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BCL6 represses a broad range of genes involved in the DNA damage response, cell cycle checkpoints, and differentiation.
“BCL6 represses a broad range of genes involved in the DNA damage response18, cell cycle checkpoints19, and differentiation20.”
From Small-molecule-induced polymerization triggers degradation of BCL6 (2020) · cites this paper as [19]
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- Authors
- Tunyaplin, C., Shaffer, A. L., Angelin-Duclos, C. D., Yu, X., Staudt, L. M., & Calame, K. L.
- Affiliations
- Columbia University (US)
- National Institutes of Health (US)
- Departments of Microbiology and Biochemistry and Molecular Biophysics, Columbia University College of Physicians and Surgeons , New York, NY 10032
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-07
- Volume
- 173
- Issue
- 2
- Pages
- 1158-1165
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1566926046
- Cited by
- 376
- References
- 37
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 8 · 2023: 18 · 2022: 13 · 2021: 15 · 2020: 17 · 2019: 16 · 2018: 12 · 2017: 10 · 2016: 18 · 2015: 29 · 2014: 24 · 2013: 16 · 2012: 18
- FWCI
- 7.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (R01 50659)
- National Institute of Allergy and Infectious Diseases (R01 AI43576, R01AI043576)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Keywords
- Blimp-1, BCL6, transcriptional repression, intronic regulatory elements, plasmacytic differentiation, B cell terminal differentiation, STAT3, antibody response
- MeSH terms
- Positive Regulatory Domain I-Binding Factor 1, Animals, Cell Transformation, Neoplastic, DNA-Binding Proteins, Humans, Plasmacytoma, Proto-Oncogene Proteins, Repressor Proteins, Transcription Factors, Trans-Activators, DNA Footprinting, STAT3 Transcription Factor, Mice, Proto-Oncogene Proteins c-bcl-6
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