BCL-6, a POZ/zinc-finger protein, is a sequence-specific transcriptional repressor

Chih Chao Chang, B. Hilda Ye, R. S K Chaganti, Riccardo Dalla-Favera

Research output: Contribution to journalArticle

368 Citations (Scopus)

Abstract

Approximately 40% of diffuse large cell lymphoma are associated with chromosomal translocations that deregulate the expression of the BCL6 gene by juxtaposing heterologous promoters to the BCL-6 coding domain. The BCL6 gene encodes a 95-kDa protein containing six C-terminal zinc-finger motifs and an N-terminal POZ domain, suggesting that it may function as a transcription factor. By using a DNA sequence selected for its ability to hind recombinant BCL-6 in vitro, we show here that BCL-6 is present in DNA-binding complexes in nuclear extracts from various B-cell lines. In transient transfection experiments, BCL6 can repress transcription from promoters linked to its DNA target sequence and this activity is dependent upon specific DNA-binding and the presence of an intact N-terminal half of the protein. We demonstrate that this part of the BCL6 molecule contains an autonomous transrepressor domain and that two noncontiguous regions, including the POZ motif, mediate maximum transrepressive activity. These results indicate that the BCL-6 protein can function as a sequence-specific transcriptional repressor and have implications for the role of BCL6 in normal lymphoid development and lymphomagenesis.

Original languageEnglish (US)
Pages (from-to)6947-6952
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number14
DOIs
StatePublished - Jul 9 1996
Externally publishedYes

Fingerprint

Zinc Fingers
Genetic Translocation
Proteins
Lymphoma, Large B-Cell, Diffuse
DNA
Transfection
B-Lymphocytes
Transcription Factors
Gene Expression
Cell Line
Genes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

BCL-6, a POZ/zinc-finger protein, is a sequence-specific transcriptional repressor. / Chang, Chih Chao; Ye, B. Hilda; Chaganti, R. S K; Dalla-Favera, Riccardo.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 14, 09.07.1996, p. 6947-6952.

Research output: Contribution to journalArticle

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AB - Approximately 40% of diffuse large cell lymphoma are associated with chromosomal translocations that deregulate the expression of the BCL6 gene by juxtaposing heterologous promoters to the BCL-6 coding domain. The BCL6 gene encodes a 95-kDa protein containing six C-terminal zinc-finger motifs and an N-terminal POZ domain, suggesting that it may function as a transcription factor. By using a DNA sequence selected for its ability to hind recombinant BCL-6 in vitro, we show here that BCL-6 is present in DNA-binding complexes in nuclear extracts from various B-cell lines. In transient transfection experiments, BCL6 can repress transcription from promoters linked to its DNA target sequence and this activity is dependent upon specific DNA-binding and the presence of an intact N-terminal half of the protein. We demonstrate that this part of the BCL6 molecule contains an autonomous transrepressor domain and that two noncontiguous regions, including the POZ motif, mediate maximum transrepressive activity. These results indicate that the BCL-6 protein can function as a sequence-specific transcriptional repressor and have implications for the role of BCL6 in normal lymphoid development and lymphomagenesis.

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