Howard Hughes Medical Institute and Programs in Gene Function and Expression and Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Annu Rev Genomics Hum Genet. 2012;13:29-57. doi: 10.1146/annurev-genom-090711-163723. Epub 2012 Jun 11.
There has been a recent surge in the use of genome-wide methodologies to identify and annotate the transcriptional regulatory elements in the human genome. Here we review some of these methodologies and the conceptual insights about transcription regulation that have been gained from the use of genome-wide studies. It has become clear that the binding of transcription factors is itself a highly regulated process, and binding does not always appear to have functional consequences. Numerous properties have now been associated with regulatory elements that may be useful in their identification. Several aspects of enhancer function have been shown to be more widespread than was previously appreciated, including the highly combinatorial nature of transcription factor binding, the postinitiation regulation of many target genes, and the binding of enhancers at early stages to maintain their competence during development. Going forward, the integration of multiple genome-wide data sets should become a standard approach to elucidate higher-order regulatory interactions.
近年来，人们越来越多地使用全基因组方法来识别和注释人类基因组中的转录调控元件。在这里，我们回顾了其中的一些方法，并讨论了通过全基因组研究获得的关于转录调控的概念性见解。很明显，转录因子的结合本身就是一个高度调控的过程，而且结合并不总是具有功能后果。现在已经有许多与调控元件相关的特性被发现，这些特性可能有助于它们的识别。已经证明，增强子的几个功能方面比以前认识到的更为广泛，包括转录因子结合的高度组合性质、许多靶基因的起始后调节，以及增强子在早期与靶基因结合以在发育过程中维持其能力。展望未来，整合多个全基因组数据集应该成为阐明更高阶调控相互作用的标准方法。
