Grove Christian A, De Masi Federico, Barrasa M Inmaculada, Newburger Daniel E, Alkema Mark J, Bulyk Martha L, Walhout Albertha J M
Program in Gene Function and Expression and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Cell. 2009 Jul 23;138(2):314-27. doi: 10.1016/j.cell.2009.04.058.
Differences in expression, protein interactions, and DNA binding of paralogous transcription factors ("TF parameters") are thought to be important determinants of regulatory and biological specificity. However, both the extent of TF divergence and the relative contribution of individual TF parameters remain undetermined. We comprehensively identify dimerization partners, spatiotemporal expression patterns, and DNA-binding specificities for the C. elegans bHLH family of TFs, and model these data into an integrated network. This network displays both specificity and promiscuity, as some bHLH proteins, DNA sequences, and tissues are highly connected, whereas others are not. By comparing all bHLH TFs, we find extensive divergence and that all three parameters contribute equally to bHLH divergence. Our approach provides a framework for examining divergence for other protein families in C. elegans and in other complex multicellular organisms, including humans. Cross-species comparisons of integrated networks may provide further insights into molecular features underlying protein family evolution. For a video summary of this article, see the PaperFlick file available with the online Supplemental Data.
同源转录因子的表达、蛋白质相互作用及DNA结合差异（“转录因子参数”）被认为是调控特异性和生物学特异性的重要决定因素。然而，转录因子的分化程度以及各个转录因子参数的相对贡献仍未确定。我们全面鉴定了秀丽隐杆线虫bHLH转录因子家族的二聚化伙伴、时空表达模式及DNA结合特异性，并将这些数据建模为一个整合网络。该网络既显示出特异性，也存在混杂性，因为一些bHLH蛋白、DNA序列和组织高度相关，而其他的则不然。通过比较所有bHLH转录因子，我们发现了广泛的分化，且所有这三个参数对bHLH分化的贡献均等。我们的方法为研究秀丽隐杆线虫及包括人类在内的其他复杂多细胞生物中其他蛋白质家族的分化提供了一个框架。整合网络的跨物种比较可能会为深入了解蛋白质家族进化的分子特征提供更多见解。有关本文的视频摘要，请参阅在线补充数据中提供的PaperFlick文件。
