Identification of Transcription Factor-Binding Sites in the Mouse FOXO1 Promoter

One critical determinant of levels of gene expression is binding of transcription factors to cognate DNA sequences in promoter and enhancer regions of target genes. Transcription factors are DNA-binding proteins to which transcriptional co-regulators are bound, ultimately resulting in histone modifications that change chromatin structure to regulate transcription. Examples of transcription factors include hormone-activated transcription factors such as the glucocorticoid receptor, transcription factors regulated by cell surface receptors such as FOXO1 and Smad2/Smad3, and many others. Promoter regions typically contain multiple, diverse transcription factor-binding sites. Binding sites for cell-type-specific transcription factors involved in cell fate determination such as Runx2, MyoD, or myogenin are frequently observed. Promoter regions are located within ~2 kb upstream of the transcriptional start site, whereas enhancers may be located at some distance from promoter sequences and exert long-range effects. Here, we will discuss classical and emerging technologies by which one can understand the role of binding of specific transcription factors in regulation of transcription of FOXO genes.