Payankaulam Sandhya, Arnosti David N
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.
Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17314-9. doi: 10.1073/pnas.0904507106. Epub 2009 Sep 28.
Despite the pervasive roles for repressors in transcriptional control, the range of action of these proteins on cis regulatory elements remains poorly understood. Knirps has essential roles in patterning the Drosophila embryo by means of short-range repression, an activity that is essential for proper regulation of complex transcriptional control elements. Short-range repressors function in a local fashion to interfere with the activity of activators or basal promoters within approximately 100 bp. In contrast, long-range repressors such as Hairy act over distances >1 kb. The functional distinction between these two classes of repressors has been suggested to stem from the differential recruitment of the CtBP corepressor to short-range repressors and Groucho to long-range repressors. Contrary to this differential recruitment model, we report that Groucho is a functional part of the Knirps short-range repression complex. The corepressor interaction is mediated via an eh-1 like motif present in the N terminus and a conserved region present in the central portion of Knirps. We also show that this interaction is important for the CtBP-independent repression activity of Knirps and is required for regulation of even-skipped. Our study uncovers a previously uncharacterized interaction between proteins previously thought to function in distinct repression pathways, and indicates that the Groucho corepressor can be differentially harnessed to execute short- and long-range repression.
尽管阻遏物在转录调控中具有普遍作用，但这些蛋白质对顺式调控元件的作用范围仍知之甚少。克尼普斯（Knirps）通过短程抑制在果蝇胚胎模式形成中发挥重要作用，这种活性对于复杂转录调控元件的正确调控至关重要。短程阻遏物以局部方式发挥作用，干扰大约100 bp内激活剂或基础启动子的活性。相比之下，像毛状蛋白（Hairy）这样的长程阻遏物作用距离大于1 kb。这两类阻遏物之间的功能差异被认为源于共抑制因子CtBP向短程阻遏物的差异募集以及Gro/TLE向长程阻遏物的差异募集。与这种差异募集模型相反，我们报告称Gro/TLE是克尼普斯短程抑制复合物的功能组成部分。共抑制因子相互作用是通过N端存在的一个类eh-1基序和克尼普斯中部存在的一个保守区域介导的。我们还表明，这种相互作用对于克尼普斯不依赖CtBP的抑制活性很重要，并且是调控偶数跳动基因（even-skipped）所必需的。我们的研究揭示了以前被认为在不同抑制途径中起作用的蛋白质之间一种以前未被表征的相互作用，并表明共抑制因子Gro/TLE可以被差异性利用来执行短程和长程抑制。
