TY - JOUR T1 - Deciphering Transcriptional Regulation of Human Core Promoters JF - bioRxiv DO - 10.1101/174904 SP - 174904 AU - Shira Weingarten-Gabbay AU - Ronit Nir AU - Shai Lubliner AU - Eilon Sharon AU - Yael Kalma AU - Adina Weinberger AU - Eran Segal Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/08/10/174904.abstract N2 - Although traditionally viewed as universal stretches of DNA, core promoters are diverse regulatory sequences with a high impact on transcriptional activity in promoters and enhancers. However, our understanding of their function, architecture, and cis-regulatory elements is still lacking. Here, we devised a high-throughput assay to quantify the core promoter activity of ∼15,000 fully designed sequences that we integrated and expressed from a fixed location within the human genome. By measuring ∼500 Pre-Initiation Complex (PIC) binding sequences, we find functional differences between promoters and enhancers and that both exhibit unidirectional activity. Our systematic investigation of all possible combinations of core promoter elements reveals a positive effect on expression of TATA and Initiator, and a negative effect of BREu and BREd. Moreover, we observe a 10bp periodicity in the optimal distance between the TATA and the Inr. By comprehensively screening TF binding-sites, we show that site orientation has little effect, that the effect of binding site number on expression is factor-specific, and that there is a striking agreement between the effect of binding site multiplicity and TF appearance in endogenous homotypic clusters. Thus, we provide a systematic view of the core- and proximal-promoter regions and shed light on organization principles of regulatory regions in the human genome. ER -