Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands.
Genome Res. 2010 Feb;20(2):190-200. doi: 10.1101/gr.098822.109. Epub 2009 Dec 9.
In eukaryotes, many chromatin proteins together regulate gene expression. Chromatin proteins often direct the genomic binding pattern of other chromatin proteins, for example, by recruitment or competition mechanisms. The network of such targeting interactions in chromatin is complex and still poorly understood. Based on genome-wide binding maps, we constructed a Bayesian network model of the targeting interactions among a broad set of 43 chromatin components in Drosophila cells. This model predicts many novel functional relationships. For example, we found that the homologous proteins HP1 and HP1C each target the heterochromatin protein HP3 to distinct sets of genes in a competitive manner. We also discovered a central role for the remodeling factor Brahma in the targeting of several DNA-binding factors, including GAGA factor, JRA, and SU(VAR)3-7. Our network model provides a global view of the targeting interplay among dozens of chromatin components.
在真核生物中，许多染色质蛋白共同调节基因表达。染色质蛋白通常通过招募或竞争机制来指导其他染色质蛋白在基因组上的结合模式。染色质中这种靶向相互作用的网络非常复杂，目前仍知之甚少。基于全基因组结合图谱，我们构建了一个贝叶斯网络模型，用于研究果蝇细胞中广泛的 43 种染色质成分之间的靶向相互作用。该模型预测了许多新的功能关系。例如，我们发现同源蛋白 HP1 和 HP1C 以竞争的方式将异染色质蛋白 HP3 靶向到不同的基因集合。我们还发现重塑因子 Brahma 在靶向包括 GAGA 因子、JRA 和 SU(VAR)3-7 在内的几个 DNA 结合因子中的核心作用。我们的网络模型提供了几十种染色质成分之间靶向相互作用的全局视图。
