Hutchins Andrew Paul, Diez Diego, Miranda-Saavedra Diego
Bioinformatics and Genomics Laboratory; World Premier International (WPI) Immunology Frontier Research Center (IFReC); Osaka University; Suita, Osaka Japan.
JAKSTAT. 2013 Oct 1;2(4):e25097. doi: 10.4161/jkst.25097. Epub 2013 May 20.
STAT3 is the quintessential pleiotropic transcription factor with many biological roles throughout development as well as in multiple adult tissues. Its functional heterogeneity is encoded in the range of genome-wide binding patterns that specify different regulatory networks in distinct cell types. However, STAT3 does not display remarkable DNA binding preferences that may help correlate specific motifs with individual biological functions or cell types. Therefore, achieving a detailed understanding of the regulatory mechanisms that endow STAT3 (or any other pleiotropic transcription factor) with such a rainbow of functions is not only a central problem in biology but also a fiendishly difficult one. Here we describe key genomic and computational approaches that have shed light into this question, and present the two current models of STAT3 binding (universal and cell type-specific). We also discuss the role that the local epigenetic environment plays in the selection of STAT3 binding sites.
信号转导和转录激活因子3（STAT3）是典型的多效性转录因子，在整个发育过程以及多种成体组织中具有多种生物学作用。其功能异质性编码于全基因组范围的结合模式中，这些模式在不同细胞类型中指定了不同的调控网络。然而，STAT3并未表现出显著的DNA结合偏好，而这种偏好可能有助于将特定基序与个体生物学功能或细胞类型相关联。因此，详细了解赋予STAT3（或任何其他多效性转录因子）如此多样功能的调控机制，不仅是生物学中的核心问题，也是极其困难的问题。在这里，我们描述了一些关键的基因组和计算方法，这些方法为这个问题提供了线索，并介绍了目前关于STAT3结合的两种模型（通用型和细胞类型特异性）。我们还讨论了局部表观遗传环境在STAT3结合位点选择中所起的作用。
