Class II histone deacetylases are directly recruited by BCL6 transcriptional repressor.
BCL6 is a member of the POZ/zinc finger (POK) family involved in survival and/or differentiation of a number of cell types and in B cell lymphoma upon chromosomal alteration. Transcriptional repression by BCL6 is thought to be achieved in part by recruiting a repressor complex containing two class I histone deacetylases (HDACs). In this study we investigated whether BCL6 could also target members of class II HDACs. Our results indicate that three related class II deacetylases, HDAC4, HDAC5, and HDAC7 can associate with BCL6 in vivo and in vitro. Using electron microscopy, we found that endogenous BCL6 and class II HDACs partially co-localize in the nucleus. Overexpression experiments showed that BCL6 and HDAC4, -5, or -7 are intermingled onto common nuclear substructures and form stable complexes. A highly conserved domain in the N-terminal region of HDAC5 and HDAC7 as well as the zinc finger region of BCL6 were found necessary for the complex formation in vivo and in vitro. Moreover, our data point to the zinc finger region of BCL6 as a multifunctional domain which, beside its known capacity to bind DNA, is involved in the nuclear targeting of the protein and in the recruitment of the class II HDACs, and hence constitutes an autonomous repressor domain. Since PLZF, a BCL6 relative, could also interact with HDAC4, -5, and 7, we suggest that class II HDACs are largely involved in the control of the POK transcription factors activity.
Pubmed ID: 11929873 RIS Download
Animals | Blotting, Western | DNA-Binding Proteins | Genes, Reporter | Histone Deacetylases | Humans | Luciferases | Lymphoma, B-Cell | Mice | Microscopy, Electron | Plasmids | Precipitin Tests | Protein Binding | Protein Structure, Tertiary | Proto-Oncogene Proteins | Proto-Oncogene Proteins c-bcl-6 | Repressor Proteins | Transcription Factors | Transfection | Tumor Cells, Cultured | Zinc Fingers