Reactivation of the G1 enhancer landscape underlies core circuitry addiction to SWI/SNF
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F24%3A00580756" target="_blank" >RIV/61388963:_____/24:00580756 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1093/nar/gkad1081" target="_blank" >https://doi.org/10.1093/nar/gkad1081</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/nar/gkad1081" target="_blank" >10.1093/nar/gkad1081</a>
Alternative languages
Result language
angličtina
Original language name
Reactivation of the G1 enhancer landscape underlies core circuitry addiction to SWI/SNF
Original language description
Several cancer core regulatory circuitries (CRCs) depend on the sustained generation of DNA accessibility by SWI/SNF chromatin remodelers. However, the window when SWI/SNF is acutely essential in these settings has not been identified. Here we used neuroblastoma (NB) cells to model and dissect the relationship between cell-cycle progression and SWI/SNF ATPase activity. We find that SWI/SNF inactivation impairs coordinated occupancy of non-pioneer CRC members at enhancers within 1 hour, rapidly breaking their autoregulation. By precisely timing inhibitor treatment following synchronization, we show that SWI/SNF is dispensable for survival in S and G2/M, but becomes acutely essential only during G1 phase. We furthermore developed a new approach to analyze the oscillating patterns of genome-wide DNA accessibility across the cell cycle, which revealed that SWI/SNF-dependent CRC binding sites are enriched at enhancers with peak accessibility during G1 phase, where they activate genes involved in cell-cycle progression. SWI/SNF inhibition strongly impairs G1-S transition and potentiates the ability of retinoids used clinically to induce cell-cycle exit. Similar cell-cycle effects in diverse SWI/SNF-addicted settings highlight G1-S transition as a common cause of SWI/SNF dependency. Our results illustrate that deeper knowledge of the temporal patterns of enhancer-related dependencies may aid the rational targeting of addicted cancers.
Czech name
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Czech description
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Classification
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
10401 - Organic chemistry
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nucleic Acids Research
ISSN
0305-1048
e-ISSN
1362-4962
Volume of the periodical
52
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
18
Pages from-to
4-21
UT code for WoS article
001106053000001
EID of the result in the Scopus database
2-s2.0-85182500830