1: Oncogene. 1996 Jun 6;12(11):2331-42. 

Transcriptional repression by the proto-oncogene BCL-6.

Seyfert VL, Allman D, He Y, Staudt LM.

Metabolism Branch, National Cancer Institute, National Institutes of Health,
Bethesda, Maryland 20892, USA.

In up to 45% of reported cases of the non-Hodgkin's lymphoma, diffuse large cell
lymphoma, there are translocations of the BCL-6 gene, which are presumed to
deregulate its expression. The BCL-6 protein, which is unmutated in these
lymphomas, contains six Kruppel-like zinc fingers at its carboxy terminus and a
121 amino acid domain at its amino terminus, termed the POZ domain, which bears
homology with amino terminal domains in a subset zinc finger transcription
factors. In this study, we tested whether BCL-6 regulates transcription and if
the POZ domain has a role in this function. The BCL-6 POZ domain, when fused to
the GAL4 DNA binding domain, strongly repressed transcriptional activation
initiated from several different promoters including the SV40 enhancer/promoter.
Repression was also observed when the fusion protein was bound at a distance of
200 bp 5' of the promoter. When the GAL4/BCL6 POZ domain fusion protein was
expressed in yeast, it was able to homodimerize in the nucleus. Nevertheless, in
contrast with mammalian cells, the fusion protein did not repress transcription.
To test the ability of the full length BC1-6 protein to repress transcription
when bound to DNA through its zinc finger DNA binding domain, high affinity
BCL-6 binding sites were selected from a pool of random oligonucleotides. Full
length BCL-6 was able to strongly repress transcription when bound to its
cognate site cloned upstream of the thymidine kinase promoter. This repression
was mediated, in large measure, by the POZ domain, although a variant of BCL-6
lacking the POZ domain was able to repress transcription modestly. The ability
of BCL-6 to function as a transcriptional repressor may contribute to its
ability to transform B lymphocytes in diffuse large cell lymphoma.

PMID: 8649773 [PubMed - indexed for MEDLINE]


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