Regulated gene expression is a major requirement for all living organisms. The requirement for complex spatio-temporal regulation is most obvious during development and differentiation, when precise gene switching choreographs the generation of many different cell types, at the right time and the right place, from a single fertilized cell. When this process goes awry, deciphering the genetic cause can provide detailed insight into mechanisms. While chroma- tin structure and the recruitment of the transcriptional machinery to proximal promoters are well understood, how far-distant enhancers direct the correct spatial and temporal control of transcription is less clear. This concept prompted us to organize a Royal Society Discussion Meeting on this topic in October 2012. The timeliness of the debate was highlighted by the publication of results from the prominently heralded ENCODE project published just a month before the meeting (http://www.nature.com/encode/#/threads). This highlighted the unexpectedly large expanse of the human genome that appears to harbour regulatory elements [1,2]. Here, we present papers from some of the speakers at this lively and exciting meeting.
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