Quality of TCR signaling determined by differential affinities of enhancers for the composite BATF-IRF4 transcription factor complex

Iwata Arifumi; Durai Vivek; Tussiwand Roxane; Briseo Carlos G.; Wu Xiaodi; Grajales-Reyes Gary E.; Egawa Takeshi; Murphy Theresa L.; Murphy Kenneth M.

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Quality of TCR signaling determined by differential affinities of enhancers for the composite BATF-IRF4 transcription factor complex

机译：通过增强剂的差异亲和力来确定复合BATF-IRF4转录因子复合物的质量

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Variable strengths of signaling via the T cell antigen receptor (TCR) can produce divergent outcomes, but the mechanism of this remains obscure. The abundance of the transcription factor IRF4 increases with TCR signal strength, but how this would induce distinct types of responses is unclear. We compared the expression of genes in the TH2 subset of helper T cells to enhancer occupancy by the BATF-IRF4 transcription factor complex at varying strengths of TCR stimulation. Genes dependent on BATF-IRF4 clustered into groups with distinct TCR sensitivities. Enhancers exhibited a spectrum of occupancy by the BATF-IRF4 ternary complex that correlated with the sensitivity of gene expression to TCR signal strength. DNA sequences immediately flanking the previously defined AICE motif controlled the affinity of BATF-IRF4 for direct binding to DNA. Analysis by the chromatin immunoprecipitation-exonuclease (ChIP-exo) method allowed the identification of a previously unknown high-affinity AICE2 motif at a human single-nucleotide polymorphism (SNP) of the gene encoding the immunomodulatory receptor CTLA-4 that was associated with resistance to autoimmunity. Thus, the affinity of different enhancers for the BATF-IRF4 complex might underlie divergent signaling outcomes in response to various strengths of TCR signaling.

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来源
《Nature immunology》 |2017年第5期|共10页
作者
Iwata Arifumi; Durai Vivek; Tussiwand Roxane; Briseo Carlos G.; Wu Xiaodi; Grajales-Reyes Gary E.; Egawa Takeshi; Murphy Theresa L.; Murphy Kenneth M.;
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作者单位

Washington Univ Sch Med Dept Pathol &

Immunol St Louis MO 63130 USA;

Washington Univ Sch Med Dept Pathol &

Immunol St Louis MO 63130 USA;

Univ Basel Dept Biomed Basel Switzerland;

Washington Univ Sch Med Dept Pathol &

Immunol St Louis MO 63130 USA;

Washington Univ Sch Med Dept Pathol &

Immunol St Louis MO 63130 USA;

Washington Univ Sch Med Dept Pathol &

Immunol St Louis MO 63130 USA;

Washington Univ Sch Med Dept Pathol &

Immunol St Louis MO 63130 USA;

Washington Univ Sch Med Dept Pathol &

Immunol St Louis MO 63130 USA;

Washington Univ Sch Med Dept Pathol &

Immunol St Louis MO 63130 USA;

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正文语种 eng
中图分类医学免疫学;
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机译：通过增强剂的差异亲和力来确定复合BATF-IRF4转录因子复合物的质量
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Quality of TCR signaling determined by differential affinities of enhancers for the composite BATF-IRF4 transcription factor complex

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