Enhancer features that drive formation of transcriptional condensates

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 s...

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Bibliographic Details
Published inbioRxiv
Main Authors Shrinivas, Krishna, Sabari, Benjamin R, Coffey, Eliot L, Klein, Isaac A, Boija, Ann, Zamudio, Alicia V, Schuijers, Jurian, Hannett, Nancy M, Sharp, Phillip A, Young, Richard A, Chakraborty, Arup K
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 17.12.2018
Subjects
Binding sites
Condensates
Deoxyribonucleic acid
DNA
Enhancers
Gene expression
Genomes
Nucleotide sequence
Valency
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Summary: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.
DOI:10.1101/495606