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Chipping at the Function of a Transcription Factor

T-bet is a T-box transcription factor that is often described as a "master regulator" of helper T cell development. It is also expressed in several other immune cell types and may play specific functional roles in each of the different cells.

To begin to address the role that T-bet plays in functionally distinct cell types, Kristin M. Beima and colleagues identified some of the genes that are directly regulated by T-bet in different cellular settings. Using the chromatin immunoprecipitation (ChIP) assay coupled to genomic microarray technology (chip) the researchers were able to pinpoint numerous promoters that are bound by T-bet in B cells. Surprisingly, the ability of T-bet to associate with the target promoters was not dependent on the cell type background. Beima et al. also discovered that the functional role for T-bet in the regulation of target gene expression is highly variable. For example, the transcription factor is absolutely required for CXCR3 expression in Th1 cells but shows no required role in CD8⁺ T cells. The authors suggest that the mechanism for these variable outcomes may involve the differential requirement for T-bet at distinct steps in transcriptional activity at each promoter. This new technology is sure to provide additional surprises regarding the function of critical transcription factors.

FOOTNOTES

See referenced article, J. Biol. Chem. 2006, 281, 11992-12000

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