Transcriptional enhancers in development and disease 英文参考文献.docVIP

Sakabe et al. Genome Biology 2012,13:238 /2012/13/1/238 RE VIE W Transcriptional enhancers in development and disease Noboru Jo Sakabe* , Daniel Savic* and Marcelo A Nobrega ? ? hundred base pairs (bp) and are composed of clusters of transcription factor binding sites (6- to 20-bp motifs) to which combinations of trans-activating and repressive factors bind in sequence-speci?c manner. ey can be located in intergenic regions, introns and exons, tens to hundreds of kilobases from their target genes ([1], reviewed in [2]). Abstract Distal transcription enhancers are cis-regulatory elements that promote gene expression, enabling spatiotemporal control of genetic programs such as those required in metazoan developmental processes. Because of their importance, their disruption can lead to disease. Although these elements have been studied for decades through careful dissection of individual examples [3], the advent of genome-wide chromatin immunoprecipitation (ChIP), an experimental technique that locates DNA sites Transcription regulation by distal enhancers Gene expression patterns in metazoans range from where speci?c proteins are bound (reviewed in [4]) widespread expression in multiple cell types, such as enabled the largely unbiased identi?cation of tens of expression of genes required for the maintenance of basic cellular functions, to complex spatiotemporal expression thousands of putative elements in a single experiment and the discovery of global patterns that are shedding of genes with pleiotropic functions. Examples of trans- light on how enhancers act (reviewed in [5]). Studies cription factors (TFs) involved in such complex regula- using this technique have con?rmed and expanded our tion are PAX6, which is crucial for development of the appreciation of the import