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Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein
Interferon (IFN) consensus sequence-binding protein/IFN regulatory factor 8 (IRF8) is a transcription factor that regulates the differentiation and function of macrophages, granulocytes, and dendritic cells through activation or repression of target genes. Although IRF8 is also expressed in lymphocy...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118063/ https://www.ncbi.nlm.nih.gov/pubmed/16380510 http://dx.doi.org/10.1084/jem.20051450 |
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author | Lee, Chang Hoon Melchers, Mark Wang, Hongsheng Torrey, Ted A. Slota, Rebecca Qi, Chen-Feng Kim, Ji Young Lugar, Patricia Kong, Hee Jeong Farrington, Lila van der Zouwen, Boris Zhou, Jeff X. Lougaris, Vassilios Lipsky, Peter E. Grammer, Amrie C. Morse, Herbert C. |
author_facet | Lee, Chang Hoon Melchers, Mark Wang, Hongsheng Torrey, Ted A. Slota, Rebecca Qi, Chen-Feng Kim, Ji Young Lugar, Patricia Kong, Hee Jeong Farrington, Lila van der Zouwen, Boris Zhou, Jeff X. Lougaris, Vassilios Lipsky, Peter E. Grammer, Amrie C. Morse, Herbert C. |
author_sort | Lee, Chang Hoon |
collection | PubMed |
description | Interferon (IFN) consensus sequence-binding protein/IFN regulatory factor 8 (IRF8) is a transcription factor that regulates the differentiation and function of macrophages, granulocytes, and dendritic cells through activation or repression of target genes. Although IRF8 is also expressed in lymphocytes, its roles in B cell and T cell maturation or function are ill defined, and few transcriptional targets are known. Gene expression profiling of human tonsillar B cells and mouse B cell lymphomas showed that IRF8 transcripts were expressed at highest levels in centroblasts, either from secondary lymphoid tissue or transformed cells. In addition, staining for IRF8 was most intense in tonsillar germinal center (GC) dark-zone centroblasts. To discover B cell genes regulated by IRF8, we transfected purified primary tonsillar B cells with enhanced green fluorescent protein–tagged IRF8, generated small interfering RNA knockdowns of IRF8 expression in a mouse B cell lymphoma cell line, and examined the effects of a null mutation of IRF8 on B cells. Each approach identified activation-induced cytidine deaminase (AICDA) and BCL6 as targets of transcriptional activation. Chromatin immunoprecipitation studies demonstrated in vivo occupancy of 5′ sequences of both genes by IRF8 protein. These results suggest previously unappreciated roles for IRF8 in the transcriptional regulation of B cell GC reactions that include direct regulation of AICDA and BCL6. |
format | Text |
id | pubmed-2118063 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21180632007-12-13 Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein Lee, Chang Hoon Melchers, Mark Wang, Hongsheng Torrey, Ted A. Slota, Rebecca Qi, Chen-Feng Kim, Ji Young Lugar, Patricia Kong, Hee Jeong Farrington, Lila van der Zouwen, Boris Zhou, Jeff X. Lougaris, Vassilios Lipsky, Peter E. Grammer, Amrie C. Morse, Herbert C. J Exp Med Articles Interferon (IFN) consensus sequence-binding protein/IFN regulatory factor 8 (IRF8) is a transcription factor that regulates the differentiation and function of macrophages, granulocytes, and dendritic cells through activation or repression of target genes. Although IRF8 is also expressed in lymphocytes, its roles in B cell and T cell maturation or function are ill defined, and few transcriptional targets are known. Gene expression profiling of human tonsillar B cells and mouse B cell lymphomas showed that IRF8 transcripts were expressed at highest levels in centroblasts, either from secondary lymphoid tissue or transformed cells. In addition, staining for IRF8 was most intense in tonsillar germinal center (GC) dark-zone centroblasts. To discover B cell genes regulated by IRF8, we transfected purified primary tonsillar B cells with enhanced green fluorescent protein–tagged IRF8, generated small interfering RNA knockdowns of IRF8 expression in a mouse B cell lymphoma cell line, and examined the effects of a null mutation of IRF8 on B cells. Each approach identified activation-induced cytidine deaminase (AICDA) and BCL6 as targets of transcriptional activation. Chromatin immunoprecipitation studies demonstrated in vivo occupancy of 5′ sequences of both genes by IRF8 protein. These results suggest previously unappreciated roles for IRF8 in the transcriptional regulation of B cell GC reactions that include direct regulation of AICDA and BCL6. The Rockefeller University Press 2006-01-23 /pmc/articles/PMC2118063/ /pubmed/16380510 http://dx.doi.org/10.1084/jem.20051450 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles Lee, Chang Hoon Melchers, Mark Wang, Hongsheng Torrey, Ted A. Slota, Rebecca Qi, Chen-Feng Kim, Ji Young Lugar, Patricia Kong, Hee Jeong Farrington, Lila van der Zouwen, Boris Zhou, Jeff X. Lougaris, Vassilios Lipsky, Peter E. Grammer, Amrie C. Morse, Herbert C. Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein |
title | Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein |
title_full | Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein |
title_fullStr | Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein |
title_full_unstemmed | Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein |
title_short | Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein |
title_sort | regulation of the germinal center gene program by interferon (ifn) regulatory factor 8/ifn consensus sequence-binding protein |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118063/ https://www.ncbi.nlm.nih.gov/pubmed/16380510 http://dx.doi.org/10.1084/jem.20051450 |
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