FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2969762476> ?p ?o ?g. }

• W2969762476 endingPage "2220" @default.
• W2969762476 startingPage "2208" @default.
• W2969762476 abstract "Abstract The epidermal growth factor receptor (EGFR) is overexpressed in numerous solid tumors and is the subject of extensive therapeutic efforts. Much of the research on EGFR is focused on protein dynamics and downstream signaling; however, few studies have explored its transcriptional regulation. Here, we identified two enhancers (CE1 and CE2) present within the first intron of the EGFR gene in models of glioblastoma (GBM) and head and neck squamous cell carcinoma (HNSCC). CE1 and CE2 contain open chromatin and H3K27Ac histone marks, enhance transcription in reporter assays, and interact with the EGFR promoter. Enhancer genetic deletion by CRISPR/Cas9 significantly reduces EGFR transcript levels, with double deletion exercising an additive effect. Targeted repression of CE1 and CE2 by dCas9-KRAB demonstrates repression of transcription similar to that of genomic deletion. We identify AP-1 transcription factor family members in concert with BET bromodomain proteins as modulators of CE1 and CE2 activity in HNSCC and GBM through de novo motif identification and validate their presence. Genetic inhibition of AP-1 or pharmacologic disruption of BET/AP-1 binding results in downregulated EGFR protein and transcript levels, confirming a role for these factors in CE1 and CE2. Our results identify and characterize these novel enhancers, shedding light on the role that epigenetic mechanisms play in regulating EGFR transcription in EGFR-dependent cancers. Implications: We identify critical constituent enhancers present in the first intron of the EGFR gene, and provide a rationale for therapeutic targeting of EGFR intron 1 enhancers through perturbation of AP-1 and BET in EGFR-positive malignancies." @default.
• W2969762476 created "2019-08-29" @default.
• W2969762476 creator A5006104859 @default.
• W2969762476 creator A5030220235 @default.
• W2969762476 creator A5039505764 @default.
• W2969762476 creator A5055451309 @default.
• W2969762476 creator A5063149358 @default.
• W2969762476 creator A5069962244 @default.
• W2969762476 creator A5072572267 @default.
• W2969762476 creator A5080403474 @default.
• W2969762476 date "2019-11-01" @default.
• W2969762476 modified "2023-09-27" @default.
• W2969762476 title "Intron 1–Mediated Regulation of EGFR Expression in EGFR-Dependent Malignancies Is Mediated by AP-1 and BET Proteins" @default.
• W2969762476 cites W1479896379 @default.
• W2969762476 cites W1546552389 @default.
• W2969762476 cites W1701439323 @default.
• W2969762476 cites W1911965864 @default.
• W2969762476 cites W1964963969 @default.
• W2969762476 cites W1965425724 @default.
• W2969762476 cites W1971578941 @default.
• W2969762476 cites W1981030303 @default.
• W2969762476 cites W1986586739 @default.
• W2969762476 cites W1987681742 @default.
• W2969762476 cites W2004966039 @default.
• W2969762476 cites W2005946075 @default.
• W2969762476 cites W2007649418 @default.
• W2969762476 cites W2011603871 @default.
• W2969762476 cites W2016661249 @default.
• W2969762476 cites W2019443090 @default.
• W2969762476 cites W2030017878 @default.
• W2969762476 cites W2036619779 @default.
• W2969762476 cites W2037143505 @default.
• W2969762476 cites W2041535798 @default.
• W2969762476 cites W2048002474 @default.
• W2969762476 cites W2060484997 @default.
• W2969762476 cites W2061701210 @default.
• W2969762476 cites W2064047613 @default.
• W2969762476 cites W2066101080 @default.
• W2969762476 cites W2070705072 @default.
• W2969762476 cites W2091465371 @default.
• W2969762476 cites W2092687362 @default.
• W2969762476 cites W2094872845 @default.
• W2969762476 cites W2098692163 @default.
• W2969762476 cites W2101749257 @default.
• W2969762476 cites W2109816625 @default.
• W2969762476 cites W2117757143 @default.
• W2969762476 cites W2120006551 @default.
• W2969762476 cites W2140407529 @default.
• W2969762476 cites W2154149901 @default.
• W2969762476 cites W2167242172 @default.
• W2969762476 cites W2224894504 @default.
• W2969762476 cites W2268752741 @default.
• W2969762476 cites W2290985779 @default.
• W2969762476 cites W2322523258 @default.
• W2969762476 cites W2521689975 @default.
• W2969762476 cites W2557493613 @default.
• W2969762476 cites W2607129810 @default.
• W2969762476 cites W2613362156 @default.
• W2969762476 cites W2730980172 @default.
• W2969762476 cites W2736974222 @default.
• W2969762476 cites W2767028788 @default.
• W2969762476 cites W2779662045 @default.
• W2969762476 cites W2783922191 @default.
• W2969762476 cites W2796366554 @default.
• W2969762476 cites W2803252816 @default.
• W2969762476 cites W2807098127 @default.
• W2969762476 cites W2808687910 @default.
• W2969762476 cites W2889423013 @default.
• W2969762476 cites W2896399042 @default.
• W2969762476 cites W2923483441 @default.
• W2969762476 cites W2927602615 @default.
• W2969762476 cites W2952632749 @default.
• W2969762476 doi "https://doi.org/10.1158/1541-7786.mcr-19-0747" @default.
• W2969762476 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6825583" @default.
• W2969762476 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31444232" @default.
• W2969762476 hasPublicationYear "2019" @default.
• W2969762476 type Work @default.
• W2969762476 sameAs 2969762476 @default.
• W2969762476 citedByCount "7" @default.
• W2969762476 countsByYear W29697624762020 @default.
• W2969762476 countsByYear W29697624762021 @default.
• W2969762476 countsByYear W29697624762023 @default.
• W2969762476 crossrefType "journal-article" @default.
• W2969762476 hasAuthorship W2969762476A5006104859 @default.
• W2969762476 hasAuthorship W2969762476A5030220235 @default.
• W2969762476 hasAuthorship W2969762476A5039505764 @default.
• W2969762476 hasAuthorship W2969762476A5055451309 @default.
• W2969762476 hasAuthorship W2969762476A5063149358 @default.
• W2969762476 hasAuthorship W2969762476A5069962244 @default.
• W2969762476 hasAuthorship W2969762476A5072572267 @default.
• W2969762476 hasAuthorship W2969762476A5080403474 @default.
• W2969762476 hasBestOaLocation W29697624761 @default.
• W2969762476 hasConcept C101762097 @default.
• W2969762476 hasConcept C104317684 @default.
• W2969762476 hasConcept C111936080 @default.
• W2969762476 hasConcept C121608353 @default.
• W2969762476 hasConcept C134320426 @default.
• W2969762476 hasConcept C150194340 @default.

• next