A chromatin-mediated mechanism for specification of conditional transcription factor targets
A chromatin-mediated mechanism for specification of conditional transcription factor targets
复制标题
DOI：
10.1038/ng1917
复制
发表时间：
2006-12-01
期刊：
影响因子：
30.8
通讯作者：
Lieb, Jason D.
中科院分区：
文献类型：
--
作者：
Buck, Michael J.;Lieb, Jason D.
生物对环境的变化作出反应，许多这种反应是在基因转录水平上启动的。在这里，我们提供了一个以前未被发现的机制，指导转录调控新的结合目标，以应对环境变化的证据。我们发现，阻遏物激活蛋白1（Rap1），酵母代谢的主调节器，结合到一个扩大的目标集后，葡萄糖耗尽，尽管蛋白质水平下降，没有证据表明翻译后修饰。计算分析预测，蛋白质能够招募染色质调节Tup1的行为，以限制Rap1的结合分布在葡萄糖的存在下。编码Tup1的基因的缺失、Tup1的招募者或由Tup1招募的染色质调节因子导致Rap1特异性地和不适当地结合到低葡萄糖靶点。这些数据，结合全基因组测量的核小体占有率和Tup1分布，提供了证据的动态目标规范的机制，协调全基因组分布的中间亲和DNA序列基序与染色质介导的调节这些网站的可访问性。
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.