Interferon Regulatory Factor 8 (IRF8) Interacts with the BCL6 Corepressor, BCOR [Gene Regulation]

October 20th, 2014 by Yoon, J., Feng, X., Kim, Y.-S., Shin, D.-M., Hatzi, K., Wang, H., Morse, H. C.

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 (ICSBP), directly targets a large number of genes in germinal center (GC) 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 alpha helical region of IRF8 and the BCL6 binding domain (BBD) of BCOR are required for this interaction. In addition, IRF8 protein interacts directly with BCL6. Using a 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 comprised of BCOR-BCL6-IRF8 modulates BCL6-associated transcriptional regulation of GC B cell function.