RT Journal Article
SR Electronic
T1 Enhancer features that drive formation of transcriptional condensates
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 495606
DO 10.1101/495606
A1 Krishna Shrinivas
A1 Benjamin R. Sabari
A1 Eliot L. Coffey
A1 Isaac A. Klein
A1 Ann Boija
A1 Alicia V. Zamudio
A1 Jurian Schuijers
A1 Nancy M. Hannett
A1 Phillip A. Sharp
A1 Richard A. Young
A1 Arup K. Chakraborty
YR 2018
UL http://biorxiv.org/content/early/2018/12/17/495606.abstract
AB Enhancers, DNA elements that regulate gene expression, contain transcription factor (TF) binding sites. TFs bind short sequence motifs that are present throughout the genome at much higher frequency than active enhancers, and so the features that define active enhancers are not well understood. We show that DNA elements with TF binding site valency, density, and binding affinity above sharply defined thresholds can recruit TFs and coactivators in condensates by the cooperative process of phase separation. We demonstrate that weak cooperative interactions between IDRs of TFs and coactivators in combination with specific TF-DNA interactions are required for forming such transcriptional condensates. IDR-IDR interactions are relatively non-specific with the same molecular interactions shared by many TFs and coactivators, and phase separation is a universal cooperative mechanism. Therefore, whether a genomic locus is an enhancer that can assemble a transcriptional condensate is determined predominantly by its cognate TFs’ binding site valency and density.