Winter Stephanie E, Campbell Gerard
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Development. 2004 Dec;131(24):6071-81. doi: 10.1242/dev.01538. Epub 2004 Nov 10.
Patterning along developing body axes is regulated by gradients of transcription factors, which activate or repress different genes above distinct thresholds. Understanding differential threshold responses requires knowledge of how these factors regulate transcription. In the Drosophila wing, expression of genes such as omb and sal along the anteroposterior axis is restricted by lateral-to-medial gradients of the transcriptional repressor Brinker (Brk). omb is less sensitive to repression by Brk than sal and is consequently expressed more laterally. Contrary to previous suggestions, we show that Brk cannot repress simply by competing with activators, but requires specific repression domains along with its DNA-binding domain. Brk possesses at least three repression domains, but these are not equivalent; one, 3R, is sufficient to repress omb but not sal. Thus, although sal and omb show quantitative differences in their response to Brk, there are qualitative differences in the mechanisms that Brk uses to repress them.
沿发育中的体轴进行模式形成是由转录因子梯度调控的,这些转录因子在不同阈值之上激活或抑制不同基因。理解差异阈值反应需要了解这些因子如何调控转录。在果蝇翅膀中,诸如omb和sal等基因沿前后轴的表达受到转录抑制因子Brinker(Brk)从外侧到内侧梯度的限制。omb对Brk抑制的敏感性低于sal,因此表达位置更靠外侧。与之前的观点相反,我们发现Brk不能仅仅通过与激活因子竞争来进行抑制,而是需要特定的抑制结构域及其DNA结合结构域。Brk至少拥有三个抑制结构域,但它们并不等同;其中一个,即3R,足以抑制omb但不能抑制sal。因此,尽管sal和omb在对Brk的反应上表现出定量差异,但Brk用于抑制它们的机制存在定性差异。