期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 27, 期 24, 页码 8510-8521出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.01615-07
关键词
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资金
- NCI NIH HHS [T32 CA009537, CA09537] Funding Source: Medline
- NIAID NIH HHS [R56 AI061061, AI061061, R01 AI061061] Funding Source: Medline
- NIGMS NIH HHS [T32 GM007270, T32 GM07270] Funding Source: Medline
Appropriate cellular differentiation and specification rely upon the ability of key developmental transcription factors to precisely establish gene expression patterns. These transcription factors often regulate epigenetic events. However, it has been unclear whether this is the only role that they play in functionally regulating developmental gene expression pathways or whether they also participate in downstream transactivation events at the same promoter. The T-box transcription factor family is important in cellular specification events in many developmental systems, and determining the molecular mechanisms by which this family regulates gene expression networks warrants attention. Here, we examine the mechanism by which T-bet, a critical T-box protein in the immune system, influences transcription. T-bet is both necessary and sufficient to induce permissive histone H3-K4 dimethyl modifications at the CXCR3 and IFN-gamma promoters. A T-bet structure-function analysis revealed that the conserved T-box domain, with a small C-terminal portion, is required for recruiting histone methyltransferase activity to promoters. Interestingly, this function is conserved in the T-box family and is necessary, but not sufficient, to induce transcription, with an independent transactivation activity also required. The requirement for two separable functional activities may ultimately contribute to the stringent role for T-box proteins in establishing specific developmental gene expression pathways.
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