Two distinct functions for the BTB domain of the CD4-differentiating factor Thpok (85.20)
| Autor: | Monica Zamisch, Lie Wang, Laura Yockey, Charles Vinson, Remy Bosselut |
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| Rok vydání: | 2010 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 184:85.20-85.20 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.184.supp.85.20 |
| Popis: | Thpok is a zinc-finger (ZF) transcription factor essential for CD4 T cell development. Thpok promotes CD4 T helper lineage commitment, in part through the repression of genes necessary for CD8 differentiation. A member of the BTB-ZF subclass of ZF transcription factors, Thpok contains two conserved motifs: a carboxy-terminal ZF DNA binding domain, and an amino-terminal BTB motif. Although the BTB domain is required for Thpok to promote CD4 lineage differentiation, its contribution to Thpok function is not clear. In vitro analyses of the BTB domain of the prototype family member, Bcl6 (B cell lymphoma 6) revealed a role of the BTB domain in oligomerization and transcriptional repression. In the present study, we examined whether the Thpok BTB domain simply serves to promote dimerization of Thpok molecules, or whether it also serves to recruit other transcriptional regulators. We generated chimeric Thpok proteins by replacing the BTB domain of Thpok with that of other family members, or with a heterologous dimerization domain. All chimeric molecules containing the BTB domains tested blocked CD8 lineage specific gene expression; in contrast, the chimeric molecule carrying a heterologous dimerization domain was only partially functional. These results indicate that the BTB domain of Thpok not only promotes dimerization but it also serves to control transcription, presumably through interactions with transcriptional corepressors. |
| Databáze: | OpenAIRE |
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