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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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 Mas
  • Proto-Oncogene Proteins c-bcl-6

Substances

  • 3' Untranslated Regions
  • BCL6 protein, human
  • Bcl6 protein, mouse
  • DNA-Binding Proteins
  • MAS1 protein, human
  • MIRN155 microRNA, human
  • MIRN361 microRNA, human
  • MicroRNAs
  • Mirn155 microRNA, mouse
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-bcl-6
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase