Figure 3. Refined map of binding motifs and enhancer activity.

(A) Discovery of additional sites through in silico mutagenesis and validation. Also see Supplementary Figure 5 A and B. (B) Examples of block mutants with gain of brain activity and additional motifs discovered using alternative FL models trained on neuronal datasets. Black arrowheads indicate gain of function. Also see Supplementary Figure 5C. (C) Final TF binding motif and activity map. Includes motifs discovered using alternative models (element FL) and degenerate motifs (marked with asterisks; elements HT1, HT2 and HT3). (D) Fraction of blocks with motif predictions, by experimentally determined function. Major loss includes full loss. (E) Number of activator and inhibitor sites as estimated from experimental data alone (marked with asterisk; NEU1 and NEU2) or from experimental data combined with model motif predictions (FL, NEU3, HT1–3), by enhancer (Methods, Supplementary Figure 5D for visual guide).