Based on their pattern of transcription initiation, regulatory elements such as promoters and enhancers are commonly grouped into ‘focused’ or ‘dispersed’. Focused initiation starts from a single or a few closely spaced sites while dispersed regulatory elements start from multiple dispersed sites. The mechanisms underlying these two modes of transcription are distinct. Focused initiation is largely dependent on core promoter elements such as the TATA box or DPE, is predominant in yeast, flies, and commonly featured in your textbook. It is well understood, in part, as in vitro transcription systems facilitated the characterization and purification of the underlying key factors and sequence elements. By contrast, dispersed promoters largely lack core promoter elements and do not faithfully transcribe in vitro. Thus, in 2023, we still do now know how dispersed initiation, and thus expression of over 75% of human genes and enhancers is regulated. We thrive to develop new experimental approaches to define the DNA motifs, transcription factors and mechanisms underlying the abundant yet little studied mode of dispersed initiation. Ultimately, it is our goal to establish a paradigm for this abundant, important, but little understood mode of human gene regulation.
Human dispersed transcription initiation:
