Genomic and computational approaches to dissect the mechanisms of STAT3's universal and cell type-specific functions.
Genomic and computational approaches to dissect the mechanisms of STAT3's universal and cell type-specific functions.
复制标题
DOI：
10.4161/jkst.25097
复制
发表时间：
2013-10-01
期刊：
影响因子：
--
通讯作者：
Miranda-Saavedra D
中科院分区：
文献类型：
--
作者：
Hutchins AP;Diez D;Miranda-Saavedra D
STAT3是一种典型的多效性转录因子，在发育过程中以及在多种成体组织中发挥着多种生物学作用。它的功能异质性编码在全基因组结合模式的范围内，这些模式在不同的细胞类型中指定不同的调控网络。然而，STAT3并没有显示出显著的DNA结合偏好，这可能有助于将特定的基序与个别生物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)如此彩虹功能的调控机制，不仅是生物学上的中心问题，也是一个极其困难的问题。在这里，我们描述了关键的基因组和计算方法，揭示了这个问题，并提出了两种目前的STAT3结合模型(通用的和细胞类型特异性的)。我们还讨论了局部表观遗传环境在选择STAT3结合位点中所起的作用。
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.