Context transcription factors establish cooperative environments and mediate enhancer communication

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F24%3A00599343" target="_blank" >RIV/61388963:_____/24:00599343 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11320/24:10502100
Result on the web
<a href="https://doi.org/10.1038/s41588-024-01892-7" target="_blank" >https://doi.org/10.1038/s41588-024-01892-7</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41588-024-01892-7" target="_blank" >10.1038/s41588-024-01892-7</a>

Result language
angličtina
Original language name
Context transcription factors establish cooperative environments and mediate enhancer communication
Original language description
Many enhancers control gene expression by assembling regulatory factor clusters, also referred to as condensates. This process is vital for facilitating enhancer communication and establishing cellular identity. However, how DNA sequence and transcription factor (TF) binding instruct the formation of high regulatory factor environments remains poorly understood. Here we developed a new approach leveraging enhancer-centric chromatin accessibility quantitative trait loci (caQTLs) to nominate regulatory factor clusters genome-wide. By analyzing TF-binding signatures within the context of caQTLs and comparing episomal versus endogenous enhancer activities, we discovered a class of regulators, 'context-only' TFs, that amplify the activity of cell type-specific caQTL-binding TFs, that is, 'context-initiator' TFs. Similar to super-enhancers, enhancers enriched for context-only TF-binding sites display high coactivator binding and sensitivity to bromodomain-inhibiting molecules. We further show that binding sites for context-only and context-initiator TFs underlie enhancer coordination, providing a mechanistic rationale for how a loose TF syntax confers regulatory specificity.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10603 - Genetics and heredity (medical genetics to be 3)

Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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