E-viri
Odprti dostop
-
Yao, Xiaosai; Tan, Jing; Lim, Kevin Junliang; Koh, Joanna; Ooi, Wen Fong; Li, Zhimei; Huang, Dachuan; Xing, Manjie; Chan, Yang Sun; Qu, James Zhengzhong; Tay, Su Ting; Wijaya, Giovani; Lam, Yue Ning; Hong, Jing Han; Lee-Lim, Ai Ping; Guan, Peiyong; Ng, Michelle Shu Wen; He, Cassandra Zhengxuan; Lin, Joyce Suling; Nandi, Tannistha; Qamra, Aditi; Xu, Chang; Myint, Swe Swe; Davies, James O J; Goh, Jian Yuan; Loh, Gary; Tan, Bryan C; Rozen, Steven G; Yu, Qiang; Tan, Iain Bee Huat; Cheng, Christopher Wai Sam; Li, Shang; Chang, Kenneth Tou En; Tan, Puay Hoon; Silver, David Lawrence; Lezhava, Alexander; Steger, Gertrud; Hughes, Jim R; Teh, Bin Tean; Tan, Patrick
Cancer discovery, 11/2017, Letnik: 7, Številka: 11Journal Article
Protein-coding mutations in clear cell renal cell carcinoma (ccRCC) have been extensively characterized, frequently involving inactivation of the von Hippel-Lindau ( ) tumor suppressor. Roles for noncoding -regulatory aberrations in ccRCC tumorigenesis, however, remain unclear. Analyzing 10 primary tumor/normal pairs and 9 cell lines across 79 chromatin profiles, we observed pervasive enhancer malfunction in ccRCC, with cognate enhancer-target genes associated with tissue-specific aspects of malignancy. Superenhancer profiling identified as a ccRCC-specific and VHL-regulated master regulator whose depletion causes near-complete tumor elimination and loss predominantly drives enhancer/superenhancer deregulation more so than promoters, with acquisition of active enhancer marks (H3K27ac, H3K4me1) near ccRCC hallmark genes. Mechanistically, VHL loss stabilizes HIF2α-HIF1β heterodimer binding at enhancers, subsequently recruiting histone acetyltransferase p300 without overtly affecting preexisting promoter-enhancer interactions. Subtype-specific driver mutations such as may thus propagate unique pathogenic dependencies in ccRCC by modulating epigenomic landscapes and cancer gene expression. Comprehensive epigenomic profiling of ccRCC establishes a compendium of somatically altered -regulatory elements, uncovering new potential targets including ZNF395, a ccRCC master regulator. Loss of , a ccRCC signature event, causes pervasive enhancer malfunction, with binding of enhancer-centric HIF2α and recruitment of histone acetyltransferase p300 at preexisting lineage-specific promoter-enhancer complexes. .
Avtor
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.