(a) Our analysis of TSSs reveals a common structure across all initiation
regions, including promoters and enhancers. In both cases, (first row) a tightly packed
(110 bp \apart) divergent TSS pair (+ strand: red, − strand: blue)
surrounded by well-positioned nucleosomes (orange), with independent pre-initiation
complexes (separate TBP (green) and Pol II ChIP-exo peaks (black), second row) and sharing
two distinct transcription factor cluster binding modes (central: green, over TSS: blue;
third row). We propose that central, activator transcription factor binding (USF1 example:
purple), in conjunction with core promoter elements, determines the positioning of the
divergent initiation sites. Finally, DNA sequence properties (not depicted here), possibly
in cooperation with other factors, determine the resulting transcript type
(stable/elongating: protein coding, unstable/terminating: uaRNA, eRNA, etc.).
(b) A model depicting possible progression of enhancer states from
chromatin marked but largely inaccessible regions (left), followed by more open regions
through transcription factor binding (center) and finally, active transcription, which
brings with it the associated chromatin marks (in particular, H3K79me2 and H3K27ac and
increased methylation levels of H3K4; right).