title: Interferon regulatory factor 8 (IRF8) interacts with the B cell lymphoma 6 (BCL6) corepressor BCOR.
abstract: B cell lymphoma 6 (BCL6) corepressor (BCOR) was discovered as a BCL6-interacting corepressor, but little is known about its other biological activities in normal B cell development and function. Previously, we found that interferon regulatory factor 8 (IRF8), also known as interferon consensus sequence-binding protein, directly targets a large number of genes in germinal center B cells including BCL6. In this study, we screened potential binding partners of IRF8 using a retrovirus-based protein complementation assay screen in a mouse pre-B cell line. We found that IRF8 interacts directly with BCOR and that the α-helical region of IRF8 and the BCL6 binding domain of BCOR are required for this interaction. In addition, IRF8 protein interacts directly with BCL6. Using an siRNA-mediated IRF8 knockdown mouse B cell lymphoma cell line, we showed that IRF8 represses Bcor and enhances Bcl6 transcription. Taken together, these data suggest that a complex comprising BCOR-BCL6-IRF8 modulates BCL6-associated transcriptional regulation of germinal center B cell function.
authors.affiliation: From the Laboratory of Immunogenetics, NIAID, National Institutes of Health, Rockville, Maryland 20852 and.
authors.forename: Jeongheon
authors.initials: J
authors.lastname: Yoon
authors.affiliation: From the Laboratory of Immunogenetics, NIAID, National Institutes of Health, Rockville, Maryland 20852 and.
authors.forename: Xianxum
authors.initials: X
authors.lastname: Feng
authors.affiliation: From the Laboratory of Immunogenetics, NIAID, National Institutes of Health, Rockville, Maryland 20852 and.
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Kim
authors.affiliation: From the Laboratory of Immunogenetics, NIAID, National Institutes of Health, Rockville, Maryland 20852 and.
authors.forename: Dong-Mi
authors.initials: DM
authors.lastname: Shin
authors.affiliation: Division of Hematology and Medical Oncology, Department of Medicine and Department of Pharmacology, Weill Cornell Medical College, New York, New York 10065.
authors.forename: Katerina
authors.initials: K
authors.lastname: Hatzi
authors.affiliation: From the Laboratory of Immunogenetics, NIAID, National Institutes of Health, Rockville, Maryland 20852 and.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Wang
authors.affiliation: From the Laboratory of Immunogenetics, NIAID, National Institutes of Health, Rockville, Maryland 20852 and hmorse@niaid.nih.gov.
authors.forename: Herbert C
authors.initials: HC
authors.lastname: Morse
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D050835:Interferon Regulatory Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D025941:Protein Interaction Mapping; D051560:Proto-Oncogene Proteins c-bcl-6; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction; D014158:Transcription, Genetic; D000099185:Interferon Regulatory Factor-8
chemical_list: D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D008156:Luciferases; D051560:Proto-Oncogene Proteins c-bcl-6; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D000099185:Interferon Regulatory Factor-8; C490010:Bcl6 protein, mouse; C553467:Bcor protein, mouse
keywords: Gene Expression; Immunology; Lymphocyte; Protein Complex; Protein-Protein Interaction; Transcription Repressor