Enhancer features that drive formation of transcriptional condensates
| Autor: | Richard A. Young, Phillip A. Sharp, Eliot L. Coffey, Jurian Schuijers, Isaac A. Klein, Benjamin R. Sabari, Arup K. Chakraborty, Alicia V. Zamudio, Ann Boija, Nancy M. Hannett, Krishna Shrinivas |
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| Rok vydání: | 2018 |
| Předmět: |
Transcription
Genetic Locus (genetics) Biology Genome Article DNA sequencing Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Transcription (biology) Coactivator Gene expression Animals Binding site Enhancer Molecular Biology Gene Transcription factor 030304 developmental biology 0303 health sciences Binding Sites Base Sequence Chemistry fungi Mouse Embryonic Stem Cells DNA Genomics Cell Biology Chromatin Cell biology DNA-Binding Proteins Enhancer Elements Genetic Gene Expression Regulation Sequence motif 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | PMC Mol Cell |
| DOI: | 10.1101/495606 |
| Popis: | © 2019 Elsevier Inc. Enhancers are DNA elements that are bound by transcription factors (TFs), which recruit coactivators and the transcriptional machinery to genes. Phase-separated condensates of TFs and coactivators have been implicated in assembling the transcription machinery at particular enhancers, yet the role of DNA sequence in this process has not been explored. We show that DNA sequences encoding TF binding site number, density, and affinity above sharply defined thresholds drive condensation of TFs and coactivators. A combination of specific structured (TF-DNA) and weak multivalent (TF-coactivator) interactions allows for condensates to form at particular genomic loci determined by the DNA sequence and the complement of expressed TFs. DNA features found to drive condensation promote enhancer activity and transcription in cells. Our study provides a framework to understand how the genome can scaffold transcriptional condensates at specific loci and how the universal phenomenon of phase separation might regulate this process. Shrinivas et al. demonstrate that specific types of motif compositions encoded in DNA drive localized formation of transcriptional condensates. These findings explain how phase separation can occur at specific genomic locations and shed light on why only some genomic loci become highly active enhancers. |
| Databáze: | OpenAIRE |
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