BCL6 positively regulates AID and germinal center gene expression via repression of miR-155.
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Basso K, Schneider C, Shen Q, Holmes AB, Setty M, Leslie C, Dalla-Favera R
BCL6 positively regulates AID and germinal center gene expression via repression of miR-155.
J Exp Med. 2012 Dec 17;209(13):2455-65. doi: 10.1084/jem.20121387. Epub 2012 Nov 19.
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- 23166356 [ View in PubMed]
- Abstract
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.