Gene expression specificity of homeobox transcription factors has remained paradoxical. WUSCHEL activates and represses CLAVATA3 transcription at lower and higher concentrations, respectively. We use computational modeling and experimental analysis to investigate the properties of the cis-regulatory module. We find that intrinsically each cis-element can only activate CLAVATA3 at a higher WUSCHEL concentration. However, together, they repress CLAVATA3 at higher WUSCHEL and activate only at lower WUSCHEL, showing that the concentration-dependent interactions among cis-elements regulate both activation and repression. Biochemical experiments show that two adjacent functional cis-elements bind WUSCHEL with higher affinity and dimerize at relatively lower levels. Moreover, increasing the distance between cis-elements prolongs WUSCHEL monomer binding window, resulting in higher CLAVATA3 activation. Our work showing a constellation of optimally spaced cis-elements of defined affinities determining activation and repression thresholds in regulating CLAVATA3 transcription provides a previously unknown mechanism of cofactor-independent regulation of transcription factor binding in mediating gene expression specificity.

中文翻译：

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通过顺式元件的集体作用进行浓度依赖性转录转换

同源框转录因子的基因表达特异性仍然自相矛盾。WUSCHEL 激活和抑制CLAVATA3分别在较低和较高浓度下转录。我们使用计算建模和实验分析来研究独联体调节模块的特性。我们发现本质上每个顺式元素只能激活CLAVATA3在较高的 WUSCHEL 浓度下。然而，他们一起压制CLAVATA3在较高的 WUSCHEL 和仅在较低的 WUSCHEL 激活，表明顺式元件之间的浓度依赖性相互作用调节激活和抑制。生化实验表明，两个相邻的功能性顺式元件以更高的亲和力结合 WUSCHEL，并以相对较低的水平二聚化。此外，增加顺式元件之间的距离会延长 WUSCHEL 单体结合窗口，从而导致更高的CLAVATA3激活。我们的工作显示了一组具有确定亲和力的最佳间隔顺式元素，这些元素决定了调节中的激活和抑制阈值CLAVATA3转录提供了一种以前未知的机制，即在介导基因表达特异性中转录因子结合的辅因子非依赖性调节。