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.
Highlights
Protein partnerships regulate specific functions of cells
We found that interferon regulatory factor 8 (IRF8) interacts directly with BCOR and that the ␣-helical region of IRF8 and the B cell lymphoma 6 (BCL6) binding domain of BCOR are required for this interaction
Mouse BCOR Binds Directly with Mouse IRF8 —To identify potential partner proteins that influence the biological function of IRF8 in B lineage cells, we screened proteins interacting directly with IRF8 using a retrovirus-based protein complementation assay [22]
Summary
Protein partnerships regulate specific functions of cells. BCOR protein-protein interactions are critical to aspects of B cell biology. Using an siRNA-mediated IRF8 knockdown mouse B cell lymphoma cell line, we showed that IRF8 represses Bcor and enhances Bcl transcription. Taken together, these data suggest that a complex comprising BCOR-BCL6IRF8 modulates BCL6-associated transcriptional regulation of germinal center B cell function. The critical function of BCL6 in GC biology is associated with the BCL6 BTB/POZ domain physically interacting with the corepressor proteins BCOR [19], NCoR, SMRT [20], Mi-2/NuRD [21], and histone deacetylase complexes to mediate its potent transrepressor activity. We identified 32 potential interaction partners that included BCOR, a transcriptional corepressor that inhibits gene expression when recruited to promoter regions by BCL6 [19]. We show that BCOR interacts directly with IRF8 and that the BCOR-IRF8 complex enhances transcriptional repression by BCL6
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
