Bcl6-dependent transcriptional repression by BAZF.

BAZF, a member of Bcl6 gene family, acts as a sequence-specific transcriptional repressor in various cells including NIH3T3 cells. The DNA-binding sequence for BAZF is the same as that for Bcl6 and the repressor activity of BAZF was also inhibited by Tricostatin A, an inhibitor of histone deacetylase, suggesting the functional homology between them. However, BAZF unlike Bcl6 cannot function as a transcriptional repressor in embryonal fibroblasts of Bcl6-deficient mice and in Bcl6-null cell lines such as K562 and WIL2-NS. The BTB/POZ domain and the middle portion of BAZF bound to the BTB/POZ domain and the middle portion of Bcl6, respectively. There is an identical 17 amino acid sequence in their middle portions and the sequence was important for the binding. Since BAZF did not directly bind to mSin3A and histone deacetylase 1 and the repressor activity of BAZF was detected in K562 cells replenished with the BTB/POZ domain or the middle portion of Bcl6, BAZF may display its transrepressor activity by recruiting an mSin3A/histone deacetylase 1 complex through association with Bcl6.