RT Journal Article
SR Electronic
T1 Transcription imparts architecture, function, and logic to enhancer units
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 818849
DO 10.1101/818849
A1 Nathaniel D Tippens
A1 Jin Liang
A1 King Y Leung
A1 Abdullah Ozer
A1 James G Booth
A1 John T Lis
A1 Haiyuan Yu
YR 2019
UL http://biorxiv.org/content/early/2019/11/07/818849.abstract
AB Distal enhancers remain one of the least understood regulatory elements with pivotal roles in development and disease. We used massively parallel reporter assays to perform functional comparisons of two leading enhancer models and find that gene-distal transcription start sites (TSSs) are robust predictors of enhancer activity with higher resolution and specificity than histone modifications. We show that active enhancer units are precisely delineated by active TSSs, validate that these boundaries are sufficient to capture enhancer function, and confirm that core promoter sequences are required for this activity. Finally, we assay pairs of adjacent units and find that their cumulative activity is best predicted by the strongest unit within the pair. Synthetic fusions of enhancer units demonstrate that adjacency imposes winner-takes-all logic, revealing a simple design for a maximum-activity filter of enhancer unit outputs. Together, our results define fundamental enhancer units and a principle of non-cooperativity between adjacent units.