BCL6 positively regulates AID and germinal center gene expression via repression of miR-155

• Published in: The Journal of experimental medicine Vol. 209; no. 13; pp. 2455 - 2465
• Main Authors: Basso, Katia, Schneider, Christof, Shen, Qiong, Holmes, Antony B., Setty, Manu, Leslie, Christina, Dalla-Favera, Riccardo
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 17.12.2012
• Subjects: 3' Untranslated Regions; Animals; B-Lymphocytes - metabolism; Base Sequence; Binding Sites - genetics; Cell Line; Cytidine Deaminase - genetics; Cytidine Deaminase - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Gene Expression Regulation; Germinal Center - cytology; Germinal Center - metabolism; HEK293 Cells; Humans; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; Proto-Oncogene Proteins c-bcl-6
• ISSN: 0022-1007; 1540-9538; 1540-9538
• DOI: 10.1084/jem.20121387

The BCL6 proto-oncogene encodes a transcriptional repressor that is required for germinal center (GC) formation and whose de-regulation is involved in lymphomagenesis. Although substantial evidence indicates that BCL6 exerts its function by repressing the transcription of hundreds of protein-coding genes, its potential role in regulating gene expression via microRNAs (miRNAs) is not known. We have identified a core of 15 miRNAs that show binding of BCL6 in their genomic loci and are down-regulated in GC B cells. Among BCL6 validated targets, miR-155 and miR-361 directly modulate AID expression, indicating that via repression of these miRNAs, BCL6 up-regulates AID. Similarly, the expression of additional genes relevant for the GC phenotype, including SPI1, IRF8, and MYB, appears to be sustained via BCL6-mediated repression of miR-155. These findings identify a novel mechanism by which BCL6, in addition to repressing protein coding genes, promotes the expression of important GC functions by repressing specific miRNAs.