| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-142 |
Sentence |
denotes |
Physical interaction between MYCN oncogene and polycomb repressive complex 2 (PRC2) in neuroblastoma: functional and therapeutic implications. |
| T2 |
143-315 |
Sentence |
denotes |
CLU (clusterin) is a tumor suppressor gene that we have previously shown to be negatively modulated by the MYCN proto-oncogene, but the mechanism of repression was unclear. |
| T3 |
316-464 |
Sentence |
denotes |
Here, we show that MYCN inhibits the expression of CLU by direct interaction with the non-canonical E box sequence CACGCG in the 5'-flanking region. |
| T4 |
465-620 |
Sentence |
denotes |
Binding of MYCN to the CLU gene induces bivalent epigenetic marks and recruitment of repressive proteins such as histone deacetylases and Polycomb members. |
| T5 |
621-747 |
Sentence |
denotes |
MYCN physically binds in vitro and in vivo to EZH2, a component of the Polycomb repressive complex 2, required to repress CLU. |
| T6 |
748-867 |
Sentence |
denotes |
Notably, EZH2 interacts with the Myc box domain 3, a segment of MYC known to be essential for its transforming effects. |
| T7 |
868-975 |
Sentence |
denotes |
The expression of CLU can be restored in MYCN-amplified cells by epigenetic drugs with therapeutic results. |
| T8 |
976-1086 |
Sentence |
denotes |
Importantly, the anticancer effects of the drugs are ablated if CLU expression is blunted by RNA interference. |
| T9 |
1087-1298 |
Sentence |
denotes |
Our study implies that MYC tumorigenesis can be effectively antagonized by epigenetic drugs that interfere with the recruitment of chromatin modifiers at repressive E boxes of tumor suppressor genes such as CLU. |
