Enhancers in development and their structural features. (a) Enhancers (colored rectangles) modularly drive gene expression at particular time points and in particular tissues (arrows) by integrating inputs (transcription factors (circles), time points when they are expressed (T1, T2, T3) and cell lineages (colors)). For example, the orange enhancers promote expression of the top two genes in liver, but at different time points (T2 and T3). The enhancer in the top gene requires binding of two transcription factors for activation in T3. (b) Schematic representation of a segment of DNA wrapped in nucleosomes displaying enhancer genomic features. Histone modifications are represented by blue, green (activating) and red (repressive) ovals attached to nucleosomes. Poised and active enhancers display different histone modifications and are associated with different trans-factors. Poised enhancers without H3K27me3 have also been identified  but are not shown for clarity. Pioneer TFs pre-specify enhancers that will become active later. Unmethylated CpG islands can be found in pre-specified but inactive enhancers. Enhancers can be located tens to hundreds of kilobases away from genes; active enhancers interact with promoters looping out intervening chromatin. eRNAs are products of transcription of active enhancer sequences by RNA polymerase II (Pol II).