背景回顾：Gene expression specificity of homeobox transcription factors has remained paradoxical. WUSCHEL activates and represses CLAVATA3 transcription at lower and higher concentrations, respectively. 

主要研究：We use computational modeling and experimental analysis to investigate the properties of the cis-regulatory module.

结果1-浓度依赖性调控： 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. 

结果2-邻近顺式元件：Biochemical experiments show that two adjacent functional cis-elements bind WUSCHEL with higher affinity and dimerize at relatively lower levels. 

结果3-顺式元件间距：Moreover, increasing the distance between cis-elements prolongs WUSCHEL monomer binding window, resulting in higher CLAVATA3 activation. 

结论：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. 

 摘 要 

Homeobox转录因子的基因表达特异性似乎是自相矛盾的。WUS能够在低浓度时激活CLV3基因的表达，而在高浓度时抑制CLV3基因的表达。作者通过计算建模和试验验证，研究了一个顺式调控模块的特性。作者发现从本质上来说，每一个顺式元件只能够在高浓度WUS条件下激活CLV3基因的表达。但是，这些元件一起的时候，却能够在高浓度WUS条件下抑制CLV3基因的表达，而仅在低浓度WUS条件下激活CLV3基因的表达，在激活和抑制功能方面均表现出浓度依赖性的互作。生化实验显示两个相邻的功能性顺式元件能够在低水平WUS浓度时，以较高亲和力结合WUS并形成二聚体。此外，增加顺式元件之间的距离延长了WUS单体结合窗口，从而导致更高的CLV3基因表达激活。本文的研究揭示了一系列最优间距的顺式元件，决定调控CLV3基因表达水平的激活和抑制的阈值，从而揭示了一个从前未知的调控机制，通过控制转录因子独立于辅因子的结合来介导基因表达的特异性调控。