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

K Basso, C Schneider, Q Shen, AB Holmes… - Journal of Experimental …, 2012 - rupress.org
K Basso, C Schneider, Q Shen, AB Holmes, M Setty, C Leslie, R Dalla-Favera
Journal of Experimental Medicine, 2012rupress.org
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 …
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.
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