STAT5 represses BCL6 expression by binding to a regulatory region frequently mutated in lymphomas.

Deregulated expression of BCL6 is a pathogenic event in many lymphomas. BCL6 blocks cellular differentiation by repressing transcription of its target genes, and this may promote tumorigenesis. Conversely, the transcription factor signal transducers and activators of transcription promotes differentiation in many systems. upregulates a number of genes repressed by BCL6, raising the possibility that duanyu18135 and BCL6 have opposing roles in transcriptional regulation. Therefore, we sought to determine the effects of duanyu18135 activation on BCL6 expression and function. We found that activation of duanyu18135 downregulates BCL6 expression in B-lymphoma cells and other hematopoietic cell lines. We identified two potential regions in the first exon and first intron of BCL6 that fell within regions of high inter-species homology, suggesting conservation of regulatory function. duanyu18135 can bind inducibly and regulate transcription at one of these regions, identifying BCL6 as a duanyu18135 target gene. Additionally, downregulation of BCL6 results in loss of BCL6 repression of its target genes, confirming that duanyu18135 is a negative regulator of BCL6 function. The duanyu18135 responsive region of the BCL6 gene is mutated frequently in B-cell lymphomas, suggesting that loss of the repressive effects of duanyu18135 on BCL6 might contribute to the pathogenesis of these cancers.

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