Deciphering cis-regulatory logic with 100 million random promoters

摘要: Predicting how transcription factors (TFs) interpret regulatory sequences to control gene expression remains a major challenge. Past studies have primarily focused on native or engineered sequences, and thus remained limited in scale. Here, we use random as an alternative, measuring the output of over 100 million synthetic yeast promoters comprised DNA. Random yield broad range reproducible levels, indicating that fortuitous binding sites DNA are functional. From these data learn models transcriptional regulation explain 94% variation test data, recapitulate organization chromatin yeast, characterize activity TFs, help refine cis-regulatory motifs. We find strand, position, helical face preferences TFs widespread depend interactions with neighboring chromatin. Such high-throughput assays provide large-scale necessary complex logic.