Buck Michael J, Lieb Jason D
Department of Biology and the Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Nat Genet. 2006 Dec;38(12):1446-51. doi: 10.1038/ng1917. Epub 2006 Nov 12.
Organisms respond to changes in their environment, and many such responses are initiated at the level of gene transcription. Here, we provide evidence for a previously undiscovered mechanism for directing transcriptional regulators to new binding targets in response to an environmental change. We show that repressor-activator protein 1 (Rap1), a master regulator of yeast metabolism, binds to an expanded target set after glucose depletion despite decreasing protein levels and no evidence of posttranslational modification. Computational analysis predicts that proteins capable of recruiting the chromatin regulator Tup1 act to restrict the binding distribution of Rap1 in the presence of glucose. Deletion of the gene(s) encoding Tup1, recruiters of Tup1 or chromatin regulators recruited by Tup1 cause Rap1 to bind specifically and inappropriately to low-glucose targets. These data, combined with whole-genome measurements of nucleosome occupancy and Tup1 distribution, provide evidence for a mechanism of dynamic target specification that coordinates the genome-wide distribution of intermediate-affinity DNA sequence motifs with chromatin-mediated regulation of accessibility to those sites.
生物体对其环境变化做出反应，许多此类反应在基因转录水平上启动。在这里，我们提供了一种以前未被发现的机制的证据，该机制可指导转录调节因子响应环境变化而靶向新的结合靶点。我们表明，酵母代谢的主要调节因子阻遏物 - 激活蛋白1（Rap1）在葡萄糖耗尽后，尽管蛋白质水平降低且没有翻译后修饰的证据，但仍与扩大的靶点集结合。计算分析预测，能够募集染色质调节因子Tup1的蛋白质在葡萄糖存在下会限制Rap1的结合分布。编码Tup1、Tup1募集蛋白或由Tup1募集的染色质调节因子的基因缺失会导致Rap1特异性且不恰当地与低葡萄糖靶点结合。这些数据，结合全基因组核小体占有率和Tup1分布的测量结果，为一种动态靶点特异性机制提供了证据，该机制将中等亲和力DNA序列基序的全基因组分布与染色质介导的对这些位点可及性的调节协调起来。
