Chromatin Immunoprecipitation Reveals p53 Binding to G-Quadruplex DNA Sequences in Myeloid Leukemia Cell Lines
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F25%3A00644606" target="_blank" >RIV/68081707:_____/25:00644606 - isvavai.cz</a>
Výsledek na webu
<a href="https://pubs.acs.org/doi/10.1021/acsbiomedchemau.4c00124" target="_blank" >https://pubs.acs.org/doi/10.1021/acsbiomedchemau.4c00124</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acsbiomedchemau.4c00124" target="_blank" >10.1021/acsbiomedchemau.4c00124</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Chromatin Immunoprecipitation Reveals p53 Binding to G-Quadruplex DNA Sequences in Myeloid Leukemia Cell Lines
Popis výsledku v původním jazyce
Clarifying functions of the p53 protein is a crucial aspect of cancer research. We analyzed the binding sites of p53 wild-type (WT) protein and its oncologically significant mutants and evaluated their transactivation properties using a functional yeast assay. Unlike the binding sites as determined in myeloid leukemia cell lines by chromatin immunoprecipitation of p53-R175H, p53-Y220C, p53-M237I, p53-R248Q, and p53-R273H mutants, the target sites of p53-WT and p53-R282W were significantly associated with putative G-quadruplex sequences (PQSs). Guanine-quadruplex (G-quadruplex or G4) formation in these sequences was evaluated by using a set of biophysical methods. G4s can modulate gene expression induced by p53. At low p53 expression level, PQS upstream of the p53-response element (RE) leads to greater gene expression induced by p53-R282W compared to that for the RE without PQS. Meanwhile, p53-WT protein expression is decreased by the PQS presence. At a high p53 expression level, the presence of PQS leads to a decreased expression of the reporter regardless of the distance and localization of the G4 from the RE.
Název v anglickém jazyce
Chromatin Immunoprecipitation Reveals p53 Binding to G-Quadruplex DNA Sequences in Myeloid Leukemia Cell Lines
Popis výsledku anglicky
Clarifying functions of the p53 protein is a crucial aspect of cancer research. We analyzed the binding sites of p53 wild-type (WT) protein and its oncologically significant mutants and evaluated their transactivation properties using a functional yeast assay. Unlike the binding sites as determined in myeloid leukemia cell lines by chromatin immunoprecipitation of p53-R175H, p53-Y220C, p53-M237I, p53-R248Q, and p53-R273H mutants, the target sites of p53-WT and p53-R282W were significantly associated with putative G-quadruplex sequences (PQSs). Guanine-quadruplex (G-quadruplex or G4) formation in these sequences was evaluated by using a set of biophysical methods. G4s can modulate gene expression induced by p53. At low p53 expression level, PQS upstream of the p53-response element (RE) leads to greater gene expression induced by p53-R282W compared to that for the RE without PQS. Meanwhile, p53-WT protein expression is decreased by the PQS presence. At a high p53 expression level, the presence of PQS leads to a decreased expression of the reporter regardless of the distance and localization of the G4 from the RE.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10608 - Biochemistry and molecular biology
Návaznosti výsledku
Projekt
<a href="/cs/project/EF15_003%2F0000477" target="_blank" >EF15_003/0000477: Strukturní gymnastika nukleových kyselin: od molekulárních principů přes biologické funkce k terapeutickým cílům.</a><br>
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2025
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
ACS Bio & Med Chem Au
ISSN
2694-2437
e-ISSN
2694-2437
Svazek periodika
5
Číslo periodika v rámci svazku
2
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
16
Strana od-do
283-298
Kód UT WoS článku
001419413000001
EID výsledku v databázi Scopus
2-s2.0-105003043137